Helen Leask, PhD

In 2020, the American Cancer Society (ACS) updated its cervical screening guidelines, proposing two major changes: start cervical cancer screening at age 25, rather than 21, and perform primary human papillomavirus (HPV) testing, instead of a Pap test. 

But a recent survey, published earlier this year, found that few clinicians are following these ACS recommendations. And the reasons are multifaceted.

First, healthcare providers in the US may be unsure how to reconcile conflicting cervical cancer screening guidelines from another major organization — the US Preventive Services Task Force (USPSTF), which published guidelines in 2018. 

Although the ACS guidelines are based on an analysis of the latest evidence, 

the recommendations challenge those from the USPSTF, which dictates insurance coverage in the US. Last year, the American College of Obstetricians and Gynecologists (ACOG) aligned its guidelines with those from the USPSTF.

The USPSTF recommends average-risk individuals start Pap, not HPV, testing at age 21, and broadens the options to primary HPV testing, Pap testing, or both together starting at age 30. The ACS, on the other hand, says primary HPV testing is the preferred screening approach from the start, which should be age 25. 

Because the ACS guidelines marked a notable departure from prevailing practice, a team of researchers from five US universities decided to find out if anyone was following them. 

The results, published in the journal Cancer in March, revealed that most healthcare providers had not changed practice.

Lead author Rebecca Perkins, MD, MSc, and colleagues found that, among the 70 respondents, few were starting screening at age 25, and none had switched to primary HPV testing. 

The survey then probed clinicians’ willingness to adopt the ACS guidelines as well as their reservations and barriers to doing so. 

Notably, more than half of the survey participants said they would be willing to adopt the ACS guidelines if the best evidence supported the changes and other professional medical organizations endorsed them.

On the age change, participants highlighted a range of benefits to moving to a later screening age, including that earlier screening may not be valuable and delaying screening could reduce overtreatment. 

One participant noted: “We know that cervical cancer is usually a slow‐growing, long‐term progressive disease that does not typically show up that early in life, and we also know that, if infected, oftentimes their immune system can fight off the virus. So, it sounds reasonable at first glance [to delay screening to age 25 years].” 

Others, however, brought up barriers to initiating screening at age 25. Some mentioned that later screening may not work for high‐risk populations and others voiced concerns about missing high‐grade precancer or cancer. “It’s not unusual for us to see women in their early 20s that have already had 10 or 15 partners. … a lot of them smoke too … they just have a lot of bad habits that put them at more risk,” one respondent noted.

On the HPV vs Pap testing front, many participants described a growing confidence in HPV tests after trying co-testing. One participant said, “Honestly, I do look more at the HPV results than the cytology. I put more faith in knowing what their HPV status is than anything.” 

The main barriers to primary HPV testing, however, included lack of autonomy when working in a large health system, concerns about the efficacy of HPV testing, and a belief that cytology was valuable.

Some clinicians were worried about missing high-grade lesions or cancer. One healthcare provider said, “My only concern with primary HPV screening is occasionally you will pick up endometrial abnormalities on a Pap that you’re not going to pick up with HPV screening.”

Logistics and finances also played a role in clinicians’ hesitancy to switch to the ACS recommendation. Labs that could handle primary HPV tests were not available to some participants, and lack of insurance coverage was a barrier for others. One respondent noted, for instance, that his institution has a “cytology infrastructure that already exists in the lab and I can’t really see them switching.” 

Many survey respondents also said they were waiting for endorsement from organizations, such as ACOG and USPSTF. “We run by the USPSTF and … ACOG. We don’t run by the ACS guidelines,” one person said. 

Finally, some participants were not aware of the ACS recommendations at all or the data behind them but said they would be willing to change to primary HPV testing in the future. 

Overall, Dr. Perkins said she was happy to see that more than half of the respondents would be willing to shift to the ACS screening guidelines, but noted that many remain reluctant to do so until the USPSTF and ACOG change their guidelines. 

“It’s really just a matter of the USPSTF and ACOG endorsing” the ACS guidelines, said Dr. Perkins, professor of obstetrics and gynecology at Boston University. 

The USPSTF is currently updating its cervical screening guidelines, which could potentially help reconcile this discord between the guidelines and close the gaps in practice patterns. 

The USPSTF’s review of the evidence, which led to the 2018 guidelines, did highlight the effectiveness of HPV testing. The review authors concluded that “the evidence was consistent across trials” that primary, high-risk HPV screening increased detection of grade 3 or worse cervical intraepithelial neoplasia in the initial round of screening “by as much as 2 to 3 times when compared with cytology.”

However, Joy Melnikow, MD, MPH, first author on the USPSTF evidence review, explained that the reviewers factored in access to HPV testing when making their final recommendations.

“The consideration was making sure that a recommendation could be inclusive of all providers and all populations and not restricting access for clinics that couldn’t afford or didn’t have the machine to do [HPV testing],” Dr. Melnikow, director of the Center for Healthcare Policy and Research and professor of family and community medicine at the University of California Davis, told this news organization.

The ACS, however, did not consider potential access problems in its analysis of the evidence.

Although the ACS evidence is “excellent,” Dr. Perkins said, “it’s really just a matter of the USPSTF and ACOG endorsing that, and then it seems like a lot of people are willing to make the change.”

Dr. Perkins reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

In 2020, the American Cancer Society (ACS) updated its cervical screening guidelines, proposing two major changes: start cervical cancer screening at age 25, rather than 21, and perform primary human papillomavirus (HPV) testing, instead of a Pap test. 

But a recent survey, published earlier this year, found that few clinicians are following these ACS recommendations. And the reasons are multifaceted.

First, healthcare providers in the US may be unsure how to reconcile conflicting cervical cancer screening guidelines from another major organization — the US Preventive Services Task Force (USPSTF), which published guidelines in 2018. 

Although the ACS guidelines are based on an analysis of the latest evidence, 

the recommendations challenge those from the USPSTF, which dictates insurance coverage in the US. Last year, the American College of Obstetricians and Gynecologists (ACOG) aligned its guidelines with those from the USPSTF.

The USPSTF recommends average-risk individuals start Pap, not HPV, testing at age 21, and broadens the options to primary HPV testing, Pap testing, or both together starting at age 30. The ACS, on the other hand, says primary HPV testing is the preferred screening approach from the start, which should be age 25. 

Because the ACS guidelines marked a notable departure from prevailing practice, a team of researchers from five US universities decided to find out if anyone was following them. 

The results, published in the journal Cancer in March, revealed that most healthcare providers had not changed practice.

Lead author Rebecca Perkins, MD, MSc, and colleagues found that, among the 70 respondents, few were starting screening at age 25, and none had switched to primary HPV testing. 

The survey then probed clinicians’ willingness to adopt the ACS guidelines as well as their reservations and barriers to doing so. 

Notably, more than half of the survey participants said they would be willing to adopt the ACS guidelines if the best evidence supported the changes and other professional medical organizations endorsed them.

On the age change, participants highlighted a range of benefits to moving to a later screening age, including that earlier screening may not be valuable and delaying screening could reduce overtreatment. 

One participant noted: “We know that cervical cancer is usually a slow‐growing, long‐term progressive disease that does not typically show up that early in life, and we also know that, if infected, oftentimes their immune system can fight off the virus. So, it sounds reasonable at first glance [to delay screening to age 25 years].” 

Others, however, brought up barriers to initiating screening at age 25. Some mentioned that later screening may not work for high‐risk populations and others voiced concerns about missing high‐grade precancer or cancer. “It’s not unusual for us to see women in their early 20s that have already had 10 or 15 partners. … a lot of them smoke too … they just have a lot of bad habits that put them at more risk,” one respondent noted.

On the HPV vs Pap testing front, many participants described a growing confidence in HPV tests after trying co-testing. One participant said, “Honestly, I do look more at the HPV results than the cytology. I put more faith in knowing what their HPV status is than anything.” 

The main barriers to primary HPV testing, however, included lack of autonomy when working in a large health system, concerns about the efficacy of HPV testing, and a belief that cytology was valuable.

Some clinicians were worried about missing high-grade lesions or cancer. One healthcare provider said, “My only concern with primary HPV screening is occasionally you will pick up endometrial abnormalities on a Pap that you’re not going to pick up with HPV screening.”

Logistics and finances also played a role in clinicians’ hesitancy to switch to the ACS recommendation. Labs that could handle primary HPV tests were not available to some participants, and lack of insurance coverage was a barrier for others. One respondent noted, for instance, that his institution has a “cytology infrastructure that already exists in the lab and I can’t really see them switching.” 

Many survey respondents also said they were waiting for endorsement from organizations, such as ACOG and USPSTF. “We run by the USPSTF and … ACOG. We don’t run by the ACS guidelines,” one person said. 

Finally, some participants were not aware of the ACS recommendations at all or the data behind them but said they would be willing to change to primary HPV testing in the future. 

Overall, Dr. Perkins said she was happy to see that more than half of the respondents would be willing to shift to the ACS screening guidelines, but noted that many remain reluctant to do so until the USPSTF and ACOG change their guidelines. 

“It’s really just a matter of the USPSTF and ACOG endorsing” the ACS guidelines, said Dr. Perkins, professor of obstetrics and gynecology at Boston University. 

The USPSTF is currently updating its cervical screening guidelines, which could potentially help reconcile this discord between the guidelines and close the gaps in practice patterns. 

The USPSTF’s review of the evidence, which led to the 2018 guidelines, did highlight the effectiveness of HPV testing. The review authors concluded that “the evidence was consistent across trials” that primary, high-risk HPV screening increased detection of grade 3 or worse cervical intraepithelial neoplasia in the initial round of screening “by as much as 2 to 3 times when compared with cytology.”

However, Joy Melnikow, MD, MPH, first author on the USPSTF evidence review, explained that the reviewers factored in access to HPV testing when making their final recommendations.

“The consideration was making sure that a recommendation could be inclusive of all providers and all populations and not restricting access for clinics that couldn’t afford or didn’t have the machine to do [HPV testing],” Dr. Melnikow, director of the Center for Healthcare Policy and Research and professor of family and community medicine at the University of California Davis, told this news organization.

The ACS, however, did not consider potential access problems in its analysis of the evidence.

Although the ACS evidence is “excellent,” Dr. Perkins said, “it’s really just a matter of the USPSTF and ACOG endorsing that, and then it seems like a lot of people are willing to make the change.”

Dr. Perkins reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

In 2020, the American Cancer Society (ACS) updated its cervical screening guidelines, proposing two major changes: start cervical cancer screening at age 25, rather than 21, and perform primary human papillomavirus (HPV) testing, instead of a Pap test. 

But a recent survey, published earlier this year, found that few clinicians are following these ACS recommendations. And the reasons are multifaceted.

First, healthcare providers in the US may be unsure how to reconcile conflicting cervical cancer screening guidelines from another major organization — the US Preventive Services Task Force (USPSTF), which published guidelines in 2018. 

Although the ACS guidelines are based on an analysis of the latest evidence, 

the recommendations challenge those from the USPSTF, which dictates insurance coverage in the US. Last year, the American College of Obstetricians and Gynecologists (ACOG) aligned its guidelines with those from the USPSTF.

The USPSTF recommends average-risk individuals start Pap, not HPV, testing at age 21, and broadens the options to primary HPV testing, Pap testing, or both together starting at age 30. The ACS, on the other hand, says primary HPV testing is the preferred screening approach from the start, which should be age 25. 

Because the ACS guidelines marked a notable departure from prevailing practice, a team of researchers from five US universities decided to find out if anyone was following them. 

The results, published in the journal Cancer in March, revealed that most healthcare providers had not changed practice.

Lead author Rebecca Perkins, MD, MSc, and colleagues found that, among the 70 respondents, few were starting screening at age 25, and none had switched to primary HPV testing. 

The survey then probed clinicians’ willingness to adopt the ACS guidelines as well as their reservations and barriers to doing so. 

Notably, more than half of the survey participants said they would be willing to adopt the ACS guidelines if the best evidence supported the changes and other professional medical organizations endorsed them.

On the age change, participants highlighted a range of benefits to moving to a later screening age, including that earlier screening may not be valuable and delaying screening could reduce overtreatment. 

One participant noted: “We know that cervical cancer is usually a slow‐growing, long‐term progressive disease that does not typically show up that early in life, and we also know that, if infected, oftentimes their immune system can fight off the virus. So, it sounds reasonable at first glance [to delay screening to age 25 years].” 

Others, however, brought up barriers to initiating screening at age 25. Some mentioned that later screening may not work for high‐risk populations and others voiced concerns about missing high‐grade precancer or cancer. “It’s not unusual for us to see women in their early 20s that have already had 10 or 15 partners. … a lot of them smoke too … they just have a lot of bad habits that put them at more risk,” one respondent noted.

On the HPV vs Pap testing front, many participants described a growing confidence in HPV tests after trying co-testing. One participant said, “Honestly, I do look more at the HPV results than the cytology. I put more faith in knowing what their HPV status is than anything.” 

The main barriers to primary HPV testing, however, included lack of autonomy when working in a large health system, concerns about the efficacy of HPV testing, and a belief that cytology was valuable.

Some clinicians were worried about missing high-grade lesions or cancer. One healthcare provider said, “My only concern with primary HPV screening is occasionally you will pick up endometrial abnormalities on a Pap that you’re not going to pick up with HPV screening.”

Logistics and finances also played a role in clinicians’ hesitancy to switch to the ACS recommendation. Labs that could handle primary HPV tests were not available to some participants, and lack of insurance coverage was a barrier for others. One respondent noted, for instance, that his institution has a “cytology infrastructure that already exists in the lab and I can’t really see them switching.” 

Many survey respondents also said they were waiting for endorsement from organizations, such as ACOG and USPSTF. “We run by the USPSTF and … ACOG. We don’t run by the ACS guidelines,” one person said. 

Finally, some participants were not aware of the ACS recommendations at all or the data behind them but said they would be willing to change to primary HPV testing in the future. 

Overall, Dr. Perkins said she was happy to see that more than half of the respondents would be willing to shift to the ACS screening guidelines, but noted that many remain reluctant to do so until the USPSTF and ACOG change their guidelines. 

“It’s really just a matter of the USPSTF and ACOG endorsing” the ACS guidelines, said Dr. Perkins, professor of obstetrics and gynecology at Boston University. 

The USPSTF is currently updating its cervical screening guidelines, which could potentially help reconcile this discord between the guidelines and close the gaps in practice patterns. 

The USPSTF’s review of the evidence, which led to the 2018 guidelines, did highlight the effectiveness of HPV testing. The review authors concluded that “the evidence was consistent across trials” that primary, high-risk HPV screening increased detection of grade 3 or worse cervical intraepithelial neoplasia in the initial round of screening “by as much as 2 to 3 times when compared with cytology.”

However, Joy Melnikow, MD, MPH, first author on the USPSTF evidence review, explained that the reviewers factored in access to HPV testing when making their final recommendations.

“The consideration was making sure that a recommendation could be inclusive of all providers and all populations and not restricting access for clinics that couldn’t afford or didn’t have the machine to do [HPV testing],” Dr. Melnikow, director of the Center for Healthcare Policy and Research and professor of family and community medicine at the University of California Davis, told this news organization.

The ACS, however, did not consider potential access problems in its analysis of the evidence.

Although the ACS evidence is “excellent,” Dr. Perkins said, “it’s really just a matter of the USPSTF and ACOG endorsing that, and then it seems like a lot of people are willing to make the change.”

Dr. Perkins reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

“Maintenance therapy is big business,” warned Benjamin Derman, MD, assistant professor of medicine at the University of Chicago. He was commenting on the financial implications of new data suggesting that physicians may need to rethink maintenance with lenalidomide (Revlimid and generics) for multiple myeloma (MM).

For more than 10 years, ongoing treatment with lenalidomide following autologous hematopoietic stem cell transplantation (ASCT) has been the unchallenged gold standard.

The new findings were from the MASTER study, published in The Lancet Haematology, along with an invited commentary by Dr. Derman. In MASTER, patients who showed no evidence of disease after transplantation and two phases of consolidation therapy had the opportunity to avoid lenalidomide maintenance.

In the lenalidomide-free group, just 9% of patients without high-risk chromosome abnormalities or just one HRCA progressed within 2 years. About 47% of patients with two or more HRCAs progressed within 2 years.

The MASTER authors concluded that modern regimens of induction plus ASCT/consolidation might be good enough for many patients. Avoiding maintenance therapy “lead to most patients with newly diagnosed multiple myeloma reaching an MRD [minimal residual disease]-free, treatment-free state with a low risk of disease progression.” They also cautioned that the approach was “not optimal” for high-risk patients.

“We have been indoctrinated into continuous therapy,” said lead author Luciano Costa, MD, professor of medicine at the University of Alabama at Birmingham. “This was a reasonable approach at the time when [induction and consolidation] therapy was not as effective.”

Lenalidomide for post-ASCT maintenance became a guideline standard following a pivotal study published in the New England Journal of Medicine in 2012. The study showed that lenalidomide maintenance after transplantation almost doubled the time to progression (P < .001) and improved survival (P = .03).

Shaji Kumar, MD, is chair of the National Comprehensive Cancer Network Multiple Myeloma Guidelines and professor of medicine at the Mayo Clinic in Rochester, Minn.

Dr. Kumar said that the MASTER results alone are not sufficient to change current guidelines because the study was a single-arm, uncontrolled, phase 2 trial. However, there are “multiple reasons why we would like to stop treatment at some point in time,” Dr. Kumar said.

“Quality of life, the financial cost, and the toxicity are three main reasons why we would like to discontinue the maintenance or give maintenance only for the amount of time that a patient needs it,” Dr. Kumar added. “So then the question comes up, how do we identify the people who need long term treatment versus the people who don’t?”

“Response” in MM is conventionally classified by criteria laid down by the International Myeloma Working Group. However, the MASTER trial made use of a different measure: MRD negativity, in which myeloma cells can no longer be detected in bone-marrow aspirate at a level of 1 in 100,000 (10^–5) or, in some studies, 1 in 1 million (10^–6).

MRD is a rare bird in oncology: A surrogate endpoint that provides answers faster than progression-free survival or overall survival but is a reliable guide to both. In 2020 a team headed by Nikhil Munshi, MD, professor of medicine at Harvard Medical School, Boston, published a large meta-analysis showing that a negative MRD in a patient with MM was significantly prognostic for both progression-free survival (hazard ratio, 0.33; P < .001) and overall survival (HR, 0.45; P < .001).

In an interview from 2022, Dr. Munshi explained that patients with MRD negativity are not necessarily “cured”: “Simply, physiologically, it means that if a patient has one [myeloma] cell in a million, that cell is going to take a much longer time to grow up to be myeloma.”

In MASTER, which was based at five U.S. academic medical centers, 81% of participants (96/118) achieved MRD negativity at the 10^–5 cutoff. Eighty-four people (71%) had two consecutive MRD-negative results and did not go on to lenalidomide maintenance. Instead, they were monitored with lab tests every 8 weeks for the first 24 weeks and every 16 weeks thereafter and assessed for any changes in MRD after 6 months and 18 months.

The median age in MASTER was 61 years, 43% were women, and 20% were non-Hispanic Black. About 20% of participants had two or more HRCAs, 37% had one HRCA, and 43% had no HRCAs. All participants had four 28-day cycles of induction with Dara-KRd (daratumumab, carfilzomib, lenalidomide, and dexamethasone). This was followed by ASCT and up to two phases of consolidation with Dara-KRd.

MASTER is not the only study to show that MRD-guided discontinuation of lenalidomide seems feasible in some patients. In November 2023, Spanish researchers published a study in Blood testing a combination of lenalidomide, dexamethasone, and ixazomib. The trial allowed MRD-negative patients to stop therapy after 2 years. Progression was 17.2% over the following 4 years in the group that dropped maintenance, which included high-risk patients. The authors concluded that their results “support the safety of maintenance therapy discontinuation in patients with negative MRD at 2 years.”

These two trials are conspicuous by their rarity.

Said Dr. Derman: “We haven’t done a great job until recently of designing trials that look into discontinuation.”

Both Dr. Derman and Dr. Costa raised the elephant in the room: industry funding.

“Maintenance therapy is big business,” said Dr. Derman. He added that he had experienced problems in the past obtaining industry funding for research that involved stopping therapy.

Dr. Costa, coauthor of the MASTER trial, agreed in part: “Most pharmaceutical companies do not embark on trials like this because they’re primarily doing registration trials.” MASTER garnered some industry funding, however, and Dr. Costa found that encouraging.

How much money is at stake? In other words, what are the financial savings if patients with zero to one HRCAs who are MRD negative start to take treatment holidays from lenalidomide maintenance?

In the United States in 2019 approximately 6,410 patients received ASCT. The MASTER publication stated that “around 85%” of newly diagnosed MM patients have zero to one HRCAs and that 73% of these patients were able to stop therapy in the trial. This suggests that, each year, approximately 4,000 new patients might be eligible to avoid lenalidomide after ASCT.

The price tag of lenalidomide is approximately $20,000 per month in the United States, according to Dr. Derman. A cohort of 4,000 patients avoiding lenalidomide each year represents lost revenue of $80 million per month or almost $1 billion per year. And this does not take into account patients already on lenalidomide from previous years – or sales outside the United States. The MM multiple research pipeline reflects a lack of enthusiasm for paring down maintenance.

There are currently 229 interventional clinical studies in MM taking place nationwide. Of these, just three trials are testing what happens when patients stop therapy in the post-ASCT setting and none of the three is sponsored by industry (NCT04108624, NCT05091372, and NCT04071457). (All data from clinicaltrials.gov; search covered phase 2, 3, or 4 studies still accruing data; descriptions hand-checked; search terms: maintenance/consolidation/post-ASCT.)

Dr. Derman said that it is “incumbent on investigators” to carry out the studies to identify who is eligible to stop therapy because industry is “probably always going to err on the side of treating more.”

Sergio Giralt, MD, head of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, New York, was an author of the key 2012 study that enshrined lenalidomide maintenance in the guidelines. Dr. Giralt expressed concerns about the single-arm design of MASTER and said he would like to see a randomized study where some patients continued treatment and others stopped.

Dr. Giralt cautioned: “If you’re MRD negative, the chances of having to deal with your disease in the next 5 years is one in five.” Physicians could certainly “have a conversation” with patients who are MRD negative about stopping therapy, but this would need to be weighed against the need for bone-marrow biopsies every 3-6 months to check progress. (In MASTER, MRD was checked at 6 and 18 months.)

Dr. Kumar believes that “we need to pursue the concept of decreasing the duration of treatment.” However, newer immunotherapies may be the answer: “Who knows? That may be the future, that we will do more of this hit-and-run approach rather than trying to keep them persistently on something.”

Dr. Derman said: “I personally think that the data is already there ... [MASTER] shows that perhaps this notion of indefinite maintenance therapy is one that really has to go by the wayside ... patients should have the option to consider with their physician [the chance to] potentially discontinue treatment.”

For 15 years, relentless lenalidomide maintenance has “quite rightly been the strongest pillar of therapy”, said Dr. Costa. “But for patients, this is not something that they easily embrace – it’s not ideal that you are going to have to take therapy for the rest of your life.”

Dr. Costa concluded: “I don’t think we had a single patient who was reluctant to stop therapy.”

Dr. Munshi reported relationships with Adaptive, Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Karyopharm, Legend, Millennium, Novartis, Pfizer, and he is the scientific founder of Oncopep and DCT. Dr. Derman disclosed ties with Janssen, Cota, and BMS. Dr. Costa reported ties with Amgen, Cota, Janssen, BMS, AbbVie, Ionis, Genentech, Sanofi, Karyopharm, AstraZeneca, Adaptive Biotechnologies, Takeda, and Pfizer. Dr. Kumar declared relationships with AbbVie, Amgen, BMS, GlaxoSmithKline, Karyopharm, Regeneron, Roche, Sanofi, Takeda, and BeiGene. Dr. Giralt reported ties with Amgen, CSL Behring, Caladrius, Celgene, Ceramedix, ExpertConnect, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharmaceuticals, Magnolia Innovation, Novartis, Omeros, Pfizer, Physicians’ Education Resource, Sanofi, TRM Oncology, and Xcenda.

“Maintenance therapy is big business,” warned Benjamin Derman, MD, assistant professor of medicine at the University of Chicago. He was commenting on the financial implications of new data suggesting that physicians may need to rethink maintenance with lenalidomide (Revlimid and generics) for multiple myeloma (MM).

For more than 10 years, ongoing treatment with lenalidomide following autologous hematopoietic stem cell transplantation (ASCT) has been the unchallenged gold standard.

The new findings were from the MASTER study, published in The Lancet Haematology, along with an invited commentary by Dr. Derman. In MASTER, patients who showed no evidence of disease after transplantation and two phases of consolidation therapy had the opportunity to avoid lenalidomide maintenance.

In the lenalidomide-free group, just 9% of patients without high-risk chromosome abnormalities or just one HRCA progressed within 2 years. About 47% of patients with two or more HRCAs progressed within 2 years.

The MASTER authors concluded that modern regimens of induction plus ASCT/consolidation might be good enough for many patients. Avoiding maintenance therapy “lead to most patients with newly diagnosed multiple myeloma reaching an MRD [minimal residual disease]-free, treatment-free state with a low risk of disease progression.” They also cautioned that the approach was “not optimal” for high-risk patients.

“We have been indoctrinated into continuous therapy,” said lead author Luciano Costa, MD, professor of medicine at the University of Alabama at Birmingham. “This was a reasonable approach at the time when [induction and consolidation] therapy was not as effective.”

Lenalidomide for post-ASCT maintenance became a guideline standard following a pivotal study published in the New England Journal of Medicine in 2012. The study showed that lenalidomide maintenance after transplantation almost doubled the time to progression (P < .001) and improved survival (P = .03).

Shaji Kumar, MD, is chair of the National Comprehensive Cancer Network Multiple Myeloma Guidelines and professor of medicine at the Mayo Clinic in Rochester, Minn.

Dr. Kumar said that the MASTER results alone are not sufficient to change current guidelines because the study was a single-arm, uncontrolled, phase 2 trial. However, there are “multiple reasons why we would like to stop treatment at some point in time,” Dr. Kumar said.

“Quality of life, the financial cost, and the toxicity are three main reasons why we would like to discontinue the maintenance or give maintenance only for the amount of time that a patient needs it,” Dr. Kumar added. “So then the question comes up, how do we identify the people who need long term treatment versus the people who don’t?”

“Response” in MM is conventionally classified by criteria laid down by the International Myeloma Working Group. However, the MASTER trial made use of a different measure: MRD negativity, in which myeloma cells can no longer be detected in bone-marrow aspirate at a level of 1 in 100,000 (10^–5) or, in some studies, 1 in 1 million (10^–6).

MRD is a rare bird in oncology: A surrogate endpoint that provides answers faster than progression-free survival or overall survival but is a reliable guide to both. In 2020 a team headed by Nikhil Munshi, MD, professor of medicine at Harvard Medical School, Boston, published a large meta-analysis showing that a negative MRD in a patient with MM was significantly prognostic for both progression-free survival (hazard ratio, 0.33; P < .001) and overall survival (HR, 0.45; P < .001).

In an interview from 2022, Dr. Munshi explained that patients with MRD negativity are not necessarily “cured”: “Simply, physiologically, it means that if a patient has one [myeloma] cell in a million, that cell is going to take a much longer time to grow up to be myeloma.”

In MASTER, which was based at five U.S. academic medical centers, 81% of participants (96/118) achieved MRD negativity at the 10^–5 cutoff. Eighty-four people (71%) had two consecutive MRD-negative results and did not go on to lenalidomide maintenance. Instead, they were monitored with lab tests every 8 weeks for the first 24 weeks and every 16 weeks thereafter and assessed for any changes in MRD after 6 months and 18 months.

The median age in MASTER was 61 years, 43% were women, and 20% were non-Hispanic Black. About 20% of participants had two or more HRCAs, 37% had one HRCA, and 43% had no HRCAs. All participants had four 28-day cycles of induction with Dara-KRd (daratumumab, carfilzomib, lenalidomide, and dexamethasone). This was followed by ASCT and up to two phases of consolidation with Dara-KRd.

MASTER is not the only study to show that MRD-guided discontinuation of lenalidomide seems feasible in some patients. In November 2023, Spanish researchers published a study in Blood testing a combination of lenalidomide, dexamethasone, and ixazomib. The trial allowed MRD-negative patients to stop therapy after 2 years. Progression was 17.2% over the following 4 years in the group that dropped maintenance, which included high-risk patients. The authors concluded that their results “support the safety of maintenance therapy discontinuation in patients with negative MRD at 2 years.”

These two trials are conspicuous by their rarity.

Said Dr. Derman: “We haven’t done a great job until recently of designing trials that look into discontinuation.”

Both Dr. Derman and Dr. Costa raised the elephant in the room: industry funding.

“Maintenance therapy is big business,” said Dr. Derman. He added that he had experienced problems in the past obtaining industry funding for research that involved stopping therapy.

Dr. Costa, coauthor of the MASTER trial, agreed in part: “Most pharmaceutical companies do not embark on trials like this because they’re primarily doing registration trials.” MASTER garnered some industry funding, however, and Dr. Costa found that encouraging.

How much money is at stake? In other words, what are the financial savings if patients with zero to one HRCAs who are MRD negative start to take treatment holidays from lenalidomide maintenance?

In the United States in 2019 approximately 6,410 patients received ASCT. The MASTER publication stated that “around 85%” of newly diagnosed MM patients have zero to one HRCAs and that 73% of these patients were able to stop therapy in the trial. This suggests that, each year, approximately 4,000 new patients might be eligible to avoid lenalidomide after ASCT.

The price tag of lenalidomide is approximately $20,000 per month in the United States, according to Dr. Derman. A cohort of 4,000 patients avoiding lenalidomide each year represents lost revenue of $80 million per month or almost $1 billion per year. And this does not take into account patients already on lenalidomide from previous years – or sales outside the United States. The MM multiple research pipeline reflects a lack of enthusiasm for paring down maintenance.

There are currently 229 interventional clinical studies in MM taking place nationwide. Of these, just three trials are testing what happens when patients stop therapy in the post-ASCT setting and none of the three is sponsored by industry (NCT04108624, NCT05091372, and NCT04071457). (All data from clinicaltrials.gov; search covered phase 2, 3, or 4 studies still accruing data; descriptions hand-checked; search terms: maintenance/consolidation/post-ASCT.)

Dr. Derman said that it is “incumbent on investigators” to carry out the studies to identify who is eligible to stop therapy because industry is “probably always going to err on the side of treating more.”

Sergio Giralt, MD, head of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, New York, was an author of the key 2012 study that enshrined lenalidomide maintenance in the guidelines. Dr. Giralt expressed concerns about the single-arm design of MASTER and said he would like to see a randomized study where some patients continued treatment and others stopped.

Dr. Giralt cautioned: “If you’re MRD negative, the chances of having to deal with your disease in the next 5 years is one in five.” Physicians could certainly “have a conversation” with patients who are MRD negative about stopping therapy, but this would need to be weighed against the need for bone-marrow biopsies every 3-6 months to check progress. (In MASTER, MRD was checked at 6 and 18 months.)

Dr. Kumar believes that “we need to pursue the concept of decreasing the duration of treatment.” However, newer immunotherapies may be the answer: “Who knows? That may be the future, that we will do more of this hit-and-run approach rather than trying to keep them persistently on something.”

Dr. Derman said: “I personally think that the data is already there ... [MASTER] shows that perhaps this notion of indefinite maintenance therapy is one that really has to go by the wayside ... patients should have the option to consider with their physician [the chance to] potentially discontinue treatment.”

For 15 years, relentless lenalidomide maintenance has “quite rightly been the strongest pillar of therapy”, said Dr. Costa. “But for patients, this is not something that they easily embrace – it’s not ideal that you are going to have to take therapy for the rest of your life.”

Dr. Costa concluded: “I don’t think we had a single patient who was reluctant to stop therapy.”

Dr. Munshi reported relationships with Adaptive, Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Karyopharm, Legend, Millennium, Novartis, Pfizer, and he is the scientific founder of Oncopep and DCT. Dr. Derman disclosed ties with Janssen, Cota, and BMS. Dr. Costa reported ties with Amgen, Cota, Janssen, BMS, AbbVie, Ionis, Genentech, Sanofi, Karyopharm, AstraZeneca, Adaptive Biotechnologies, Takeda, and Pfizer. Dr. Kumar declared relationships with AbbVie, Amgen, BMS, GlaxoSmithKline, Karyopharm, Regeneron, Roche, Sanofi, Takeda, and BeiGene. Dr. Giralt reported ties with Amgen, CSL Behring, Caladrius, Celgene, Ceramedix, ExpertConnect, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharmaceuticals, Magnolia Innovation, Novartis, Omeros, Pfizer, Physicians’ Education Resource, Sanofi, TRM Oncology, and Xcenda.

“Maintenance therapy is big business,” warned Benjamin Derman, MD, assistant professor of medicine at the University of Chicago. He was commenting on the financial implications of new data suggesting that physicians may need to rethink maintenance with lenalidomide (Revlimid and generics) for multiple myeloma (MM).

For more than 10 years, ongoing treatment with lenalidomide following autologous hematopoietic stem cell transplantation (ASCT) has been the unchallenged gold standard.

The new findings were from the MASTER study, published in The Lancet Haematology, along with an invited commentary by Dr. Derman. In MASTER, patients who showed no evidence of disease after transplantation and two phases of consolidation therapy had the opportunity to avoid lenalidomide maintenance.

In the lenalidomide-free group, just 9% of patients without high-risk chromosome abnormalities or just one HRCA progressed within 2 years. About 47% of patients with two or more HRCAs progressed within 2 years.

The MASTER authors concluded that modern regimens of induction plus ASCT/consolidation might be good enough for many patients. Avoiding maintenance therapy “lead to most patients with newly diagnosed multiple myeloma reaching an MRD [minimal residual disease]-free, treatment-free state with a low risk of disease progression.” They also cautioned that the approach was “not optimal” for high-risk patients.

“We have been indoctrinated into continuous therapy,” said lead author Luciano Costa, MD, professor of medicine at the University of Alabama at Birmingham. “This was a reasonable approach at the time when [induction and consolidation] therapy was not as effective.”

Lenalidomide for post-ASCT maintenance became a guideline standard following a pivotal study published in the New England Journal of Medicine in 2012. The study showed that lenalidomide maintenance after transplantation almost doubled the time to progression (P < .001) and improved survival (P = .03).

Shaji Kumar, MD, is chair of the National Comprehensive Cancer Network Multiple Myeloma Guidelines and professor of medicine at the Mayo Clinic in Rochester, Minn.

Dr. Kumar said that the MASTER results alone are not sufficient to change current guidelines because the study was a single-arm, uncontrolled, phase 2 trial. However, there are “multiple reasons why we would like to stop treatment at some point in time,” Dr. Kumar said.

“Quality of life, the financial cost, and the toxicity are three main reasons why we would like to discontinue the maintenance or give maintenance only for the amount of time that a patient needs it,” Dr. Kumar added. “So then the question comes up, how do we identify the people who need long term treatment versus the people who don’t?”

“Response” in MM is conventionally classified by criteria laid down by the International Myeloma Working Group. However, the MASTER trial made use of a different measure: MRD negativity, in which myeloma cells can no longer be detected in bone-marrow aspirate at a level of 1 in 100,000 (10^–5) or, in some studies, 1 in 1 million (10^–6).

MRD is a rare bird in oncology: A surrogate endpoint that provides answers faster than progression-free survival or overall survival but is a reliable guide to both. In 2020 a team headed by Nikhil Munshi, MD, professor of medicine at Harvard Medical School, Boston, published a large meta-analysis showing that a negative MRD in a patient with MM was significantly prognostic for both progression-free survival (hazard ratio, 0.33; P < .001) and overall survival (HR, 0.45; P < .001).

In an interview from 2022, Dr. Munshi explained that patients with MRD negativity are not necessarily “cured”: “Simply, physiologically, it means that if a patient has one [myeloma] cell in a million, that cell is going to take a much longer time to grow up to be myeloma.”

In MASTER, which was based at five U.S. academic medical centers, 81% of participants (96/118) achieved MRD negativity at the 10^–5 cutoff. Eighty-four people (71%) had two consecutive MRD-negative results and did not go on to lenalidomide maintenance. Instead, they were monitored with lab tests every 8 weeks for the first 24 weeks and every 16 weeks thereafter and assessed for any changes in MRD after 6 months and 18 months.

The median age in MASTER was 61 years, 43% were women, and 20% were non-Hispanic Black. About 20% of participants had two or more HRCAs, 37% had one HRCA, and 43% had no HRCAs. All participants had four 28-day cycles of induction with Dara-KRd (daratumumab, carfilzomib, lenalidomide, and dexamethasone). This was followed by ASCT and up to two phases of consolidation with Dara-KRd.

MASTER is not the only study to show that MRD-guided discontinuation of lenalidomide seems feasible in some patients. In November 2023, Spanish researchers published a study in Blood testing a combination of lenalidomide, dexamethasone, and ixazomib. The trial allowed MRD-negative patients to stop therapy after 2 years. Progression was 17.2% over the following 4 years in the group that dropped maintenance, which included high-risk patients. The authors concluded that their results “support the safety of maintenance therapy discontinuation in patients with negative MRD at 2 years.”

These two trials are conspicuous by their rarity.

Said Dr. Derman: “We haven’t done a great job until recently of designing trials that look into discontinuation.”

Both Dr. Derman and Dr. Costa raised the elephant in the room: industry funding.

“Maintenance therapy is big business,” said Dr. Derman. He added that he had experienced problems in the past obtaining industry funding for research that involved stopping therapy.

Dr. Costa, coauthor of the MASTER trial, agreed in part: “Most pharmaceutical companies do not embark on trials like this because they’re primarily doing registration trials.” MASTER garnered some industry funding, however, and Dr. Costa found that encouraging.

How much money is at stake? In other words, what are the financial savings if patients with zero to one HRCAs who are MRD negative start to take treatment holidays from lenalidomide maintenance?

In the United States in 2019 approximately 6,410 patients received ASCT. The MASTER publication stated that “around 85%” of newly diagnosed MM patients have zero to one HRCAs and that 73% of these patients were able to stop therapy in the trial. This suggests that, each year, approximately 4,000 new patients might be eligible to avoid lenalidomide after ASCT.

The price tag of lenalidomide is approximately $20,000 per month in the United States, according to Dr. Derman. A cohort of 4,000 patients avoiding lenalidomide each year represents lost revenue of $80 million per month or almost $1 billion per year. And this does not take into account patients already on lenalidomide from previous years – or sales outside the United States. The MM multiple research pipeline reflects a lack of enthusiasm for paring down maintenance.

There are currently 229 interventional clinical studies in MM taking place nationwide. Of these, just three trials are testing what happens when patients stop therapy in the post-ASCT setting and none of the three is sponsored by industry (NCT04108624, NCT05091372, and NCT04071457). (All data from clinicaltrials.gov; search covered phase 2, 3, or 4 studies still accruing data; descriptions hand-checked; search terms: maintenance/consolidation/post-ASCT.)

Dr. Derman said that it is “incumbent on investigators” to carry out the studies to identify who is eligible to stop therapy because industry is “probably always going to err on the side of treating more.”

Sergio Giralt, MD, head of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, New York, was an author of the key 2012 study that enshrined lenalidomide maintenance in the guidelines. Dr. Giralt expressed concerns about the single-arm design of MASTER and said he would like to see a randomized study where some patients continued treatment and others stopped.

Dr. Giralt cautioned: “If you’re MRD negative, the chances of having to deal with your disease in the next 5 years is one in five.” Physicians could certainly “have a conversation” with patients who are MRD negative about stopping therapy, but this would need to be weighed against the need for bone-marrow biopsies every 3-6 months to check progress. (In MASTER, MRD was checked at 6 and 18 months.)

Dr. Kumar believes that “we need to pursue the concept of decreasing the duration of treatment.” However, newer immunotherapies may be the answer: “Who knows? That may be the future, that we will do more of this hit-and-run approach rather than trying to keep them persistently on something.”

Dr. Derman said: “I personally think that the data is already there ... [MASTER] shows that perhaps this notion of indefinite maintenance therapy is one that really has to go by the wayside ... patients should have the option to consider with their physician [the chance to] potentially discontinue treatment.”

For 15 years, relentless lenalidomide maintenance has “quite rightly been the strongest pillar of therapy”, said Dr. Costa. “But for patients, this is not something that they easily embrace – it’s not ideal that you are going to have to take therapy for the rest of your life.”

Dr. Costa concluded: “I don’t think we had a single patient who was reluctant to stop therapy.”

Dr. Munshi reported relationships with Adaptive, Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Karyopharm, Legend, Millennium, Novartis, Pfizer, and he is the scientific founder of Oncopep and DCT. Dr. Derman disclosed ties with Janssen, Cota, and BMS. Dr. Costa reported ties with Amgen, Cota, Janssen, BMS, AbbVie, Ionis, Genentech, Sanofi, Karyopharm, AstraZeneca, Adaptive Biotechnologies, Takeda, and Pfizer. Dr. Kumar declared relationships with AbbVie, Amgen, BMS, GlaxoSmithKline, Karyopharm, Regeneron, Roche, Sanofi, Takeda, and BeiGene. Dr. Giralt reported ties with Amgen, CSL Behring, Caladrius, Celgene, Ceramedix, ExpertConnect, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharmaceuticals, Magnolia Innovation, Novartis, Omeros, Pfizer, Physicians’ Education Resource, Sanofi, TRM Oncology, and Xcenda.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Several new clinical trials in prostate cancer have opened in recent months. Maybe one of your patients is eligible to participate?

Prostate cancer at high risk for biochemical recurrence following radical prostatectomy and/or radiation therapy. Adult patients with this diagnosis can join a randomized, double-blind, placebo-controlled, phase 3 study evaluating darolutamide (Nubeqa) plus androgen deprivation therapy against ADT alone. For up to 2 years, one group of participants will take twice-daily tablets of darolutamide, a nonsteroidal antiandrogen approved in 2019, in combination with ADT. A second group will take placebo plus ADT. Sites in California, Colorado, and worldwide started recruiting for 750 participants in April 2023; study centers across 19 other states in the US are gearing up. The primary outcome measure is radiological progression-free survival (PFS). Overall survival and quality of life (QoL) are secondary measures. More details at clinicaltrials.gov.

Commenting on the study, Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, said the trial “addresses an important question regarding intensification of androgen deprivation therapy with darolutamide” – specifically, whether this intensified approach is useful for a large proportion of men who experience biochemical recurrence (BCR) – rising PSA levels – after definitive localized therapy.

Dr. Garnick cautioned, however, that “it will be very important for the study investigators to stratify the many characteristics of BCR – and not treat this population as a homogeneous one since initial Gleason Score, time to BCR, and PSA doubling time all may impact the outcomes.”

Metastatic castration-sensitive prostate cancer. Adults with this type of cancer can join a randomized, open-label, phase 3 trial evaluating the nonsteroidal antiandrogen apalutamide (Erleada). Apalutamide, the first treatment approved for nonmetastatic castration-resistant prostate cancer, has also been approved for patients with metastatic castration-sensitive prostate cancer. This new trial will assess an intermittent approach to providing ADT alongside apalutamide in patients with metastatic disease.

All participants will take daily apalutamide tablets plus physician’s choice of ADT for 6 months. Everyone whose PSA falls below 0.2 ng/mL will either receive apalutamide with intermittent ADT per protocol or continue to receive apalutamide plus ADT for a further 18 months or until the patient discontinues the study, whichever happens first. Recruitment of 333 participants is planned for sites in Colorado, New York, Ohio, Utah, and Germany starting in August 2023. Radiographic PFS and hot flash score are the primary endpoints. QoL and overall survival are secondary outcomes. See more details at clinicaltrials.gov.

This study “should add to our knowledge of optimal treatment” for metastatic castrate-sensitive prostate cancer,” Dr. Garnick said. However, “this is a very heterogeneous population of patients and how they get to the [diagnosis] of metastatic castrate-sensitive prostate cancer is important. The sample size and stratifications need to be well studied for this study to provide any meaningful data.”

Localized intermediate- or high-risk prostate cancer. People with one of these clinical scenarios who have not yet had stereotactic body radiation therapy (SBRT) or a prostatectomy are eligible for a randomized, open-label, phase 2 study. This National Cancer Institute (NCI) trial is looking at whether the experimental immunocytokine M9241 can enhance the effectiveness of SBRT. M9241 is designed to assist the immune system to fight cancer by boosting the activity of T cells at necrotic sites in the tumor.

All participants will receive standard of care ADT. One group of people will also receive three subcutaneous injections of M9241 at 4-weekly intervals in deescalating doses, then 10 days of standard SBRT, followed by another three injections of M9241 at the highest tolerable dose. A second group will only undergo SBRT. The National Institutes of Health Clinical Center in Bethesda, Maryland, started recruiting the trial’s 65 participants in June 2023. The primary endpoints are the doses of M9241 in combination with ADT that are safe and tolerable, and T-cell clonality (a measure of immunologic activity). Overall survival and QoL will not be tracked. More details are available at clinicaltrials.gov.

“The M9241 study is very important,” said Dr. Garnick, explaining that he hopes the trial will add to the growing knowledge about the interactions of radiation and its effects on the immune system.

Confirmed prostate cancer. People with prostate cancer eligible for triplet or doublet ADT combination therapy can join a randomized, single-masked, phase 2 NCI investigation of bright white light therapy for ADT-associated fatigue and depression. All participants will receive standard of care ADT combination therapy for up to a year. One group of participants will use AYOpro glasses, a commercial bright white light therapy, daily as ADT starts (“immediate” therapy). A second set of people will start using the glasses after 6 months of ADT therapy (“delayed” therapy). The City of Hope Medical Center, Duarte, Calif., planned to start welcoming the trial’s 210 participants in August 2023. Fatigue is the primary endpoint, QoL is a secondary endpoint, and overall survival will not be recorded. More details are available at clinicaltrials.gov.

“Fatigue is an important feature of cancer therapies in general and any approach to lessen the impact of fatigue should be welcome,” Dr. Garnick said. However, “it would have been helpful” if the official description of the trial had provided more information on the rationale for testing bright white light therapy in prostate cancer.

Metastatic castration-resistant prostate cancer. Adults with this diagnosis who have been treated with one prior androgen receptor axis-targeted therapy (ARAT) can enter a randomized, open-label, phase 2 trial to determine the best dose of the antibody-drug conjugate vobramitamab duocarmazine (MacroGenics). This experimental drug is designed to deliver an alkylating agent that promotes cell death in solid tumors expressing B7-H3. The B7-H3 protein rarely appears in normal tissues but is expressed at high frequency in 60% of cancers.

For approximately 2 years, participants will receive one of two doses of intravenous vobramitamab duocarmazine every 4 weeks. The trial opened in June 2023, looking to recruit 100 participants across nine states in the United States and eight other countries. The primary outcome measure is radiographic PFS. Overall survival and QoL will not be assessed. More details at clinicaltrials.gov.

Localized or biochemically recurrent prostate cancer. Adults in this position who have not received prior GnRH agonist or antagonist therapy are being recruited for a randomized, single-masked, phase 2 study comparing QoL among patients taking ADTs relugolix (Orgovyx, Relumina) and leuprolide acetate for depot suspension (Lupron Depot). For up to 1 year, people in the trial will either take daily tablets of relugolix or receive injections of leuprolide every 3 months. Three study sites in Massachusetts are due to open their doors in August 2023, seeking 110 participants. The study will assess various measures of QoL. Overall survival will not be measured. More details at clinicaltrials.gov.

This study is “sort of plain vanilla,” Dr. Garnick said. Although “the objectives of the study are important, the study number is small and unlikely to show any meaningful differences,” even if differences do exist.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov). Dr. Garnick reported no relevant financial relationships. He is editor-in-chief of the Harvard Medical School Annual Report on Prostate Diseases, for which he receives an honorarium. 

A version of this article first appeared on Medscape.com.

Several new clinical trials in prostate cancer have opened in recent months. Maybe one of your patients is eligible to participate?

Prostate cancer at high risk for biochemical recurrence following radical prostatectomy and/or radiation therapy. Adult patients with this diagnosis can join a randomized, double-blind, placebo-controlled, phase 3 study evaluating darolutamide (Nubeqa) plus androgen deprivation therapy against ADT alone. For up to 2 years, one group of participants will take twice-daily tablets of darolutamide, a nonsteroidal antiandrogen approved in 2019, in combination with ADT. A second group will take placebo plus ADT. Sites in California, Colorado, and worldwide started recruiting for 750 participants in April 2023; study centers across 19 other states in the US are gearing up. The primary outcome measure is radiological progression-free survival (PFS). Overall survival and quality of life (QoL) are secondary measures. More details at clinicaltrials.gov.

Commenting on the study, Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, said the trial “addresses an important question regarding intensification of androgen deprivation therapy with darolutamide” – specifically, whether this intensified approach is useful for a large proportion of men who experience biochemical recurrence (BCR) – rising PSA levels – after definitive localized therapy.

Dr. Garnick cautioned, however, that “it will be very important for the study investigators to stratify the many characteristics of BCR – and not treat this population as a homogeneous one since initial Gleason Score, time to BCR, and PSA doubling time all may impact the outcomes.”

Metastatic castration-sensitive prostate cancer. Adults with this type of cancer can join a randomized, open-label, phase 3 trial evaluating the nonsteroidal antiandrogen apalutamide (Erleada). Apalutamide, the first treatment approved for nonmetastatic castration-resistant prostate cancer, has also been approved for patients with metastatic castration-sensitive prostate cancer. This new trial will assess an intermittent approach to providing ADT alongside apalutamide in patients with metastatic disease.

All participants will take daily apalutamide tablets plus physician’s choice of ADT for 6 months. Everyone whose PSA falls below 0.2 ng/mL will either receive apalutamide with intermittent ADT per protocol or continue to receive apalutamide plus ADT for a further 18 months or until the patient discontinues the study, whichever happens first. Recruitment of 333 participants is planned for sites in Colorado, New York, Ohio, Utah, and Germany starting in August 2023. Radiographic PFS and hot flash score are the primary endpoints. QoL and overall survival are secondary outcomes. See more details at clinicaltrials.gov.

This study “should add to our knowledge of optimal treatment” for metastatic castrate-sensitive prostate cancer,” Dr. Garnick said. However, “this is a very heterogeneous population of patients and how they get to the [diagnosis] of metastatic castrate-sensitive prostate cancer is important. The sample size and stratifications need to be well studied for this study to provide any meaningful data.”

Localized intermediate- or high-risk prostate cancer. People with one of these clinical scenarios who have not yet had stereotactic body radiation therapy (SBRT) or a prostatectomy are eligible for a randomized, open-label, phase 2 study. This National Cancer Institute (NCI) trial is looking at whether the experimental immunocytokine M9241 can enhance the effectiveness of SBRT. M9241 is designed to assist the immune system to fight cancer by boosting the activity of T cells at necrotic sites in the tumor.

All participants will receive standard of care ADT. One group of people will also receive three subcutaneous injections of M9241 at 4-weekly intervals in deescalating doses, then 10 days of standard SBRT, followed by another three injections of M9241 at the highest tolerable dose. A second group will only undergo SBRT. The National Institutes of Health Clinical Center in Bethesda, Maryland, started recruiting the trial’s 65 participants in June 2023. The primary endpoints are the doses of M9241 in combination with ADT that are safe and tolerable, and T-cell clonality (a measure of immunologic activity). Overall survival and QoL will not be tracked. More details are available at clinicaltrials.gov.

“The M9241 study is very important,” said Dr. Garnick, explaining that he hopes the trial will add to the growing knowledge about the interactions of radiation and its effects on the immune system.

Confirmed prostate cancer. People with prostate cancer eligible for triplet or doublet ADT combination therapy can join a randomized, single-masked, phase 2 NCI investigation of bright white light therapy for ADT-associated fatigue and depression. All participants will receive standard of care ADT combination therapy for up to a year. One group of participants will use AYOpro glasses, a commercial bright white light therapy, daily as ADT starts (“immediate” therapy). A second set of people will start using the glasses after 6 months of ADT therapy (“delayed” therapy). The City of Hope Medical Center, Duarte, Calif., planned to start welcoming the trial’s 210 participants in August 2023. Fatigue is the primary endpoint, QoL is a secondary endpoint, and overall survival will not be recorded. More details are available at clinicaltrials.gov.

“Fatigue is an important feature of cancer therapies in general and any approach to lessen the impact of fatigue should be welcome,” Dr. Garnick said. However, “it would have been helpful” if the official description of the trial had provided more information on the rationale for testing bright white light therapy in prostate cancer.

Metastatic castration-resistant prostate cancer. Adults with this diagnosis who have been treated with one prior androgen receptor axis-targeted therapy (ARAT) can enter a randomized, open-label, phase 2 trial to determine the best dose of the antibody-drug conjugate vobramitamab duocarmazine (MacroGenics). This experimental drug is designed to deliver an alkylating agent that promotes cell death in solid tumors expressing B7-H3. The B7-H3 protein rarely appears in normal tissues but is expressed at high frequency in 60% of cancers.

For approximately 2 years, participants will receive one of two doses of intravenous vobramitamab duocarmazine every 4 weeks. The trial opened in June 2023, looking to recruit 100 participants across nine states in the United States and eight other countries. The primary outcome measure is radiographic PFS. Overall survival and QoL will not be assessed. More details at clinicaltrials.gov.

Localized or biochemically recurrent prostate cancer. Adults in this position who have not received prior GnRH agonist or antagonist therapy are being recruited for a randomized, single-masked, phase 2 study comparing QoL among patients taking ADTs relugolix (Orgovyx, Relumina) and leuprolide acetate for depot suspension (Lupron Depot). For up to 1 year, people in the trial will either take daily tablets of relugolix or receive injections of leuprolide every 3 months. Three study sites in Massachusetts are due to open their doors in August 2023, seeking 110 participants. The study will assess various measures of QoL. Overall survival will not be measured. More details at clinicaltrials.gov.

This study is “sort of plain vanilla,” Dr. Garnick said. Although “the objectives of the study are important, the study number is small and unlikely to show any meaningful differences,” even if differences do exist.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov). Dr. Garnick reported no relevant financial relationships. He is editor-in-chief of the Harvard Medical School Annual Report on Prostate Diseases, for which he receives an honorarium. 

A version of this article first appeared on Medscape.com.

Several new clinical trials in prostate cancer have opened in recent months. Maybe one of your patients is eligible to participate?

Prostate cancer at high risk for biochemical recurrence following radical prostatectomy and/or radiation therapy. Adult patients with this diagnosis can join a randomized, double-blind, placebo-controlled, phase 3 study evaluating darolutamide (Nubeqa) plus androgen deprivation therapy against ADT alone. For up to 2 years, one group of participants will take twice-daily tablets of darolutamide, a nonsteroidal antiandrogen approved in 2019, in combination with ADT. A second group will take placebo plus ADT. Sites in California, Colorado, and worldwide started recruiting for 750 participants in April 2023; study centers across 19 other states in the US are gearing up. The primary outcome measure is radiological progression-free survival (PFS). Overall survival and quality of life (QoL) are secondary measures. More details at clinicaltrials.gov.

Commenting on the study, Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, said the trial “addresses an important question regarding intensification of androgen deprivation therapy with darolutamide” – specifically, whether this intensified approach is useful for a large proportion of men who experience biochemical recurrence (BCR) – rising PSA levels – after definitive localized therapy.

Dr. Garnick cautioned, however, that “it will be very important for the study investigators to stratify the many characteristics of BCR – and not treat this population as a homogeneous one since initial Gleason Score, time to BCR, and PSA doubling time all may impact the outcomes.”

Metastatic castration-sensitive prostate cancer. Adults with this type of cancer can join a randomized, open-label, phase 3 trial evaluating the nonsteroidal antiandrogen apalutamide (Erleada). Apalutamide, the first treatment approved for nonmetastatic castration-resistant prostate cancer, has also been approved for patients with metastatic castration-sensitive prostate cancer. This new trial will assess an intermittent approach to providing ADT alongside apalutamide in patients with metastatic disease.

All participants will take daily apalutamide tablets plus physician’s choice of ADT for 6 months. Everyone whose PSA falls below 0.2 ng/mL will either receive apalutamide with intermittent ADT per protocol or continue to receive apalutamide plus ADT for a further 18 months or until the patient discontinues the study, whichever happens first. Recruitment of 333 participants is planned for sites in Colorado, New York, Ohio, Utah, and Germany starting in August 2023. Radiographic PFS and hot flash score are the primary endpoints. QoL and overall survival are secondary outcomes. See more details at clinicaltrials.gov.

This study “should add to our knowledge of optimal treatment” for metastatic castrate-sensitive prostate cancer,” Dr. Garnick said. However, “this is a very heterogeneous population of patients and how they get to the [diagnosis] of metastatic castrate-sensitive prostate cancer is important. The sample size and stratifications need to be well studied for this study to provide any meaningful data.”

Localized intermediate- or high-risk prostate cancer. People with one of these clinical scenarios who have not yet had stereotactic body radiation therapy (SBRT) or a prostatectomy are eligible for a randomized, open-label, phase 2 study. This National Cancer Institute (NCI) trial is looking at whether the experimental immunocytokine M9241 can enhance the effectiveness of SBRT. M9241 is designed to assist the immune system to fight cancer by boosting the activity of T cells at necrotic sites in the tumor.

All participants will receive standard of care ADT. One group of people will also receive three subcutaneous injections of M9241 at 4-weekly intervals in deescalating doses, then 10 days of standard SBRT, followed by another three injections of M9241 at the highest tolerable dose. A second group will only undergo SBRT. The National Institutes of Health Clinical Center in Bethesda, Maryland, started recruiting the trial’s 65 participants in June 2023. The primary endpoints are the doses of M9241 in combination with ADT that are safe and tolerable, and T-cell clonality (a measure of immunologic activity). Overall survival and QoL will not be tracked. More details are available at clinicaltrials.gov.

“The M9241 study is very important,” said Dr. Garnick, explaining that he hopes the trial will add to the growing knowledge about the interactions of radiation and its effects on the immune system.

Confirmed prostate cancer. People with prostate cancer eligible for triplet or doublet ADT combination therapy can join a randomized, single-masked, phase 2 NCI investigation of bright white light therapy for ADT-associated fatigue and depression. All participants will receive standard of care ADT combination therapy for up to a year. One group of participants will use AYOpro glasses, a commercial bright white light therapy, daily as ADT starts (“immediate” therapy). A second set of people will start using the glasses after 6 months of ADT therapy (“delayed” therapy). The City of Hope Medical Center, Duarte, Calif., planned to start welcoming the trial’s 210 participants in August 2023. Fatigue is the primary endpoint, QoL is a secondary endpoint, and overall survival will not be recorded. More details are available at clinicaltrials.gov.

“Fatigue is an important feature of cancer therapies in general and any approach to lessen the impact of fatigue should be welcome,” Dr. Garnick said. However, “it would have been helpful” if the official description of the trial had provided more information on the rationale for testing bright white light therapy in prostate cancer.

Metastatic castration-resistant prostate cancer. Adults with this diagnosis who have been treated with one prior androgen receptor axis-targeted therapy (ARAT) can enter a randomized, open-label, phase 2 trial to determine the best dose of the antibody-drug conjugate vobramitamab duocarmazine (MacroGenics). This experimental drug is designed to deliver an alkylating agent that promotes cell death in solid tumors expressing B7-H3. The B7-H3 protein rarely appears in normal tissues but is expressed at high frequency in 60% of cancers.

For approximately 2 years, participants will receive one of two doses of intravenous vobramitamab duocarmazine every 4 weeks. The trial opened in June 2023, looking to recruit 100 participants across nine states in the United States and eight other countries. The primary outcome measure is radiographic PFS. Overall survival and QoL will not be assessed. More details at clinicaltrials.gov.

Localized or biochemically recurrent prostate cancer. Adults in this position who have not received prior GnRH agonist or antagonist therapy are being recruited for a randomized, single-masked, phase 2 study comparing QoL among patients taking ADTs relugolix (Orgovyx, Relumina) and leuprolide acetate for depot suspension (Lupron Depot). For up to 1 year, people in the trial will either take daily tablets of relugolix or receive injections of leuprolide every 3 months. Three study sites in Massachusetts are due to open their doors in August 2023, seeking 110 participants. The study will assess various measures of QoL. Overall survival will not be measured. More details at clinicaltrials.gov.

This study is “sort of plain vanilla,” Dr. Garnick said. Although “the objectives of the study are important, the study number is small and unlikely to show any meaningful differences,” even if differences do exist.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov). Dr. Garnick reported no relevant financial relationships. He is editor-in-chief of the Harvard Medical School Annual Report on Prostate Diseases, for which he receives an honorarium. 

A version of this article first appeared on Medscape.com.

A year before the COVID-19 pandemic began, a team of clinical statisticians at the University of Texas MD Anderson Cancer Center sat together in small office for a year, painstakingly hand coding data from the U.S. clinical trials database, www.clinicaltrials.gov.

They were trying to answer a simple question: Why are cancer-drug trials enrolling too few patients over the age of 65?

More than 300 trials and 262,354 patients later, the research team confirmed that participants in clinical trials were, on average, 6.5 years younger than the population for whom the drug was intended.

Ethan Ludmir_TX_web.jpg

“We found marked disparities across different disease sites. ... The patients that are enrolling on studies are markedly younger than the average patient seen in the population with those same conditions,” said team leader Ethan Ludmir, MD, assistant professor, Division of Radiation Oncology at the University of Texas.

And this age disparity was significantly greater in industry-funded trials.

Researchers have known for 20 years that cancer trial participants are not representative of the wider cancer population, and numerous government guidance documents have been issued on the matter. However, this Texas team’s findings were the first unambiguous evidence that pharmaceutical companies seem to be selecting younger patients to test their drugs.

“If we’re being generous then perhaps the answer is: They’re looking for some element of homogeneity, which is to say they don’t want competing risks to make the signal-to-noise ratio uninterpretable,” said Dr. Ludmir.

Dr. Laura Bothwell, PhD, assistant professor, Yale School of Public Health, recently coauthored a 259-page consensus report for the National Academies of Sciences, Engineering and Medicine on how to increase the research involvement of under-represented groups.

Dr. Bothwell said, “The problem with industry funded research is that ... it’s an inevitable conflict of interest that exists. They want the research to show that their products work. And older populations ... have a lot more complications, which leads to potentially less favorable results.”

The MD Anderson findings were published in JAMA Oncology. “That was the starting point in our journey,” said Dr. Ludmir. For the next 3 years, the researchers mined their painstakingly constructed database to understand what was preventing greater numbers of older patients from enrollment in cancer trials.

Meanwhile, answers were coming from elsewhere. In parallel with the work at MD Anderson, a team in California led by Mina Sedrak, MD, a medical oncologist at the City of Hope National Medical Center, had also started investigating age disparities in clinical trials.

Sedrak_Mina_CA_web.jpg

Dr. Sedrak, who also serves as deputy director of Clinical Trials at the Center for Cancer and Aging, said he had become increasingly concerned that he did not have adequate information on new cancer therapies for his older patients.

“I was caring for a large number of people who were ... older adults,” said Dr. Sedrak, “But the data that was being used to get the standard-of-care treatment for cancer did not include older adults. And so there was this lack of applicability.”

He summed up the challenges in a 2021 review paper: “Most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients.”

By 2030, it is estimated that 70% of all new cancer diagnoses will be in patients 65 years old and older. By contrast, patients over age 65 still account for only 40% of patients in cancer trials registered with the FDA (2015 figures) and older adults make up only 44% of participants in practice-changing cancer trials, according to a 2022 study.

So what is going on? Are studies specifically designed to squeeze out older patients?

Surprisingly, patients are not being kept out of trials by formal age limits, according to Dr. Ludmir. His team found that only 10% of phase 3 trials over the past 30 years had an upper limit for age, and age restrictions have been dropping by 1% a year. (For example, 16% of trials that enrolled in 2002-2005 had an upper age limit, compared with just 8% of trials that started in 2010-2014.)

Dr. Sedrak’s team found that “clinician bias” may be a factor, a situation in which trial investigators – particularly academic oncologists – are subconsciously picking younger, healthier patients for trials and excluding older, sicker patients to protect them from drug toxicities.

Dr. Ludmir said this was understandable, especially in the case of industry-driven trials, which tend to have demanding endpoints and “an overall posture of more treatment aggressiveness.”

“These are typically not trials where they’re saying, `Hey, if we add acupuncture ... are we going to see improved patient reported outcomes?’” Dr. Ludmir explained. “You’re asking ... I’ve got this cocktail of two pretty rough chemos: I want to see what happens if I add an immunotherapy to that. If I’m the clinician in clinic, I might reasonably, subconsciously, say, is the 75-year-old really who I want on this?”

What about patient bias? Perhaps fewer older patients wish to join clinical trials?

Not so, at least not at community cancer centers, said Dr. Sedrak. His team’s analysis of the National Cancer Institute Community Oncology Research Program database for 2016-2019 revealed that older patients were just as keen as the younger patients to participate in trials (68% of patients aged 50-69 years and 65% of patients 70+; P = .28).

However, drug companies may be excluding older patients by more subtle means. One-fifth of patients over 65 have had a prior cancer. Dr. Ludmir and coauthor Roshal Patel, MD, used their hand-coded www.clinicaltrials.gov database to look at prior malignancy exclusion criteria (PMEC). The analysis found “pervasive utilization” of PMEC in phase 3 trials, cropping up in 41% of studies over the past 30 years.

PMEC was significantly associated with age disparities and was significantly more common in industry-funded trials.

When asked whether PMEC are “age restriction by stealth” on the part of drug companies, Dr. Ludmir was reluctant to assign blame, but stood by his data: “The wider you restrict people in terms of having a prior cancer, the wider the age disparities in the subsequent studies, which to me is about as strong, in terms of causal understanding of these phenomena, as you can reasonably get at this level.”

In March the FDA released a guidance document titled Inclusion of Older Adults in Cancer Clinical Trials. However, its recommendations are “nonbinding” and “do not have the force and effect of law.”

To fix the issues, said Dr. Sedrak, the FDA must be given teeth.

“Okay, you write guidelines,” he said. “But if you don’t actually hold people accountable to following the guidelines, how are we going to implement and make sure that we’re transforming policy into action?”

Dr. Bothwell of Yale’s School of Public Health agreed. “Accountability has been the weakest link for decades now.”

She concluded, “In medicine there’s a tendency to believe that a therapy, because it exists and it has been tested and it’s shown some efficacy, it’s useful. But we don’t know the answer to that question unless we have statistically valid research in the population that we’re using it in.”

Dr. Bothwell and Dr. Ludmir report no conflicts of interest. In his publications, Dr. Sedrak reports industry grants from Seattle Genetics, Eli Lilly, Novartis, and Pfizer Foundation.
 

A year before the COVID-19 pandemic began, a team of clinical statisticians at the University of Texas MD Anderson Cancer Center sat together in small office for a year, painstakingly hand coding data from the U.S. clinical trials database, www.clinicaltrials.gov.

They were trying to answer a simple question: Why are cancer-drug trials enrolling too few patients over the age of 65?

More than 300 trials and 262,354 patients later, the research team confirmed that participants in clinical trials were, on average, 6.5 years younger than the population for whom the drug was intended.

Ethan Ludmir_TX_web.jpg

“We found marked disparities across different disease sites. ... The patients that are enrolling on studies are markedly younger than the average patient seen in the population with those same conditions,” said team leader Ethan Ludmir, MD, assistant professor, Division of Radiation Oncology at the University of Texas.

And this age disparity was significantly greater in industry-funded trials.

Researchers have known for 20 years that cancer trial participants are not representative of the wider cancer population, and numerous government guidance documents have been issued on the matter. However, this Texas team’s findings were the first unambiguous evidence that pharmaceutical companies seem to be selecting younger patients to test their drugs.

“If we’re being generous then perhaps the answer is: They’re looking for some element of homogeneity, which is to say they don’t want competing risks to make the signal-to-noise ratio uninterpretable,” said Dr. Ludmir.

Dr. Laura Bothwell, PhD, assistant professor, Yale School of Public Health, recently coauthored a 259-page consensus report for the National Academies of Sciences, Engineering and Medicine on how to increase the research involvement of under-represented groups.

Dr. Bothwell said, “The problem with industry funded research is that ... it’s an inevitable conflict of interest that exists. They want the research to show that their products work. And older populations ... have a lot more complications, which leads to potentially less favorable results.”

The MD Anderson findings were published in JAMA Oncology. “That was the starting point in our journey,” said Dr. Ludmir. For the next 3 years, the researchers mined their painstakingly constructed database to understand what was preventing greater numbers of older patients from enrollment in cancer trials.

Meanwhile, answers were coming from elsewhere. In parallel with the work at MD Anderson, a team in California led by Mina Sedrak, MD, a medical oncologist at the City of Hope National Medical Center, had also started investigating age disparities in clinical trials.

Sedrak_Mina_CA_web.jpg

Dr. Sedrak, who also serves as deputy director of Clinical Trials at the Center for Cancer and Aging, said he had become increasingly concerned that he did not have adequate information on new cancer therapies for his older patients.

“I was caring for a large number of people who were ... older adults,” said Dr. Sedrak, “But the data that was being used to get the standard-of-care treatment for cancer did not include older adults. And so there was this lack of applicability.”

He summed up the challenges in a 2021 review paper: “Most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients.”

By 2030, it is estimated that 70% of all new cancer diagnoses will be in patients 65 years old and older. By contrast, patients over age 65 still account for only 40% of patients in cancer trials registered with the FDA (2015 figures) and older adults make up only 44% of participants in practice-changing cancer trials, according to a 2022 study.

So what is going on? Are studies specifically designed to squeeze out older patients?

Surprisingly, patients are not being kept out of trials by formal age limits, according to Dr. Ludmir. His team found that only 10% of phase 3 trials over the past 30 years had an upper limit for age, and age restrictions have been dropping by 1% a year. (For example, 16% of trials that enrolled in 2002-2005 had an upper age limit, compared with just 8% of trials that started in 2010-2014.)

Dr. Sedrak’s team found that “clinician bias” may be a factor, a situation in which trial investigators – particularly academic oncologists – are subconsciously picking younger, healthier patients for trials and excluding older, sicker patients to protect them from drug toxicities.

Dr. Ludmir said this was understandable, especially in the case of industry-driven trials, which tend to have demanding endpoints and “an overall posture of more treatment aggressiveness.”

“These are typically not trials where they’re saying, `Hey, if we add acupuncture ... are we going to see improved patient reported outcomes?’” Dr. Ludmir explained. “You’re asking ... I’ve got this cocktail of two pretty rough chemos: I want to see what happens if I add an immunotherapy to that. If I’m the clinician in clinic, I might reasonably, subconsciously, say, is the 75-year-old really who I want on this?”

What about patient bias? Perhaps fewer older patients wish to join clinical trials?

Not so, at least not at community cancer centers, said Dr. Sedrak. His team’s analysis of the National Cancer Institute Community Oncology Research Program database for 2016-2019 revealed that older patients were just as keen as the younger patients to participate in trials (68% of patients aged 50-69 years and 65% of patients 70+; P = .28).

However, drug companies may be excluding older patients by more subtle means. One-fifth of patients over 65 have had a prior cancer. Dr. Ludmir and coauthor Roshal Patel, MD, used their hand-coded www.clinicaltrials.gov database to look at prior malignancy exclusion criteria (PMEC). The analysis found “pervasive utilization” of PMEC in phase 3 trials, cropping up in 41% of studies over the past 30 years.

PMEC was significantly associated with age disparities and was significantly more common in industry-funded trials.

When asked whether PMEC are “age restriction by stealth” on the part of drug companies, Dr. Ludmir was reluctant to assign blame, but stood by his data: “The wider you restrict people in terms of having a prior cancer, the wider the age disparities in the subsequent studies, which to me is about as strong, in terms of causal understanding of these phenomena, as you can reasonably get at this level.”

In March the FDA released a guidance document titled Inclusion of Older Adults in Cancer Clinical Trials. However, its recommendations are “nonbinding” and “do not have the force and effect of law.”

To fix the issues, said Dr. Sedrak, the FDA must be given teeth.

“Okay, you write guidelines,” he said. “But if you don’t actually hold people accountable to following the guidelines, how are we going to implement and make sure that we’re transforming policy into action?”

Dr. Bothwell of Yale’s School of Public Health agreed. “Accountability has been the weakest link for decades now.”

She concluded, “In medicine there’s a tendency to believe that a therapy, because it exists and it has been tested and it’s shown some efficacy, it’s useful. But we don’t know the answer to that question unless we have statistically valid research in the population that we’re using it in.”

Dr. Bothwell and Dr. Ludmir report no conflicts of interest. In his publications, Dr. Sedrak reports industry grants from Seattle Genetics, Eli Lilly, Novartis, and Pfizer Foundation.
 

A year before the COVID-19 pandemic began, a team of clinical statisticians at the University of Texas MD Anderson Cancer Center sat together in small office for a year, painstakingly hand coding data from the U.S. clinical trials database, www.clinicaltrials.gov.

They were trying to answer a simple question: Why are cancer-drug trials enrolling too few patients over the age of 65?

More than 300 trials and 262,354 patients later, the research team confirmed that participants in clinical trials were, on average, 6.5 years younger than the population for whom the drug was intended.

Ethan Ludmir_TX_web.jpg

“We found marked disparities across different disease sites. ... The patients that are enrolling on studies are markedly younger than the average patient seen in the population with those same conditions,” said team leader Ethan Ludmir, MD, assistant professor, Division of Radiation Oncology at the University of Texas.

And this age disparity was significantly greater in industry-funded trials.

Researchers have known for 20 years that cancer trial participants are not representative of the wider cancer population, and numerous government guidance documents have been issued on the matter. However, this Texas team’s findings were the first unambiguous evidence that pharmaceutical companies seem to be selecting younger patients to test their drugs.

“If we’re being generous then perhaps the answer is: They’re looking for some element of homogeneity, which is to say they don’t want competing risks to make the signal-to-noise ratio uninterpretable,” said Dr. Ludmir.

Dr. Laura Bothwell, PhD, assistant professor, Yale School of Public Health, recently coauthored a 259-page consensus report for the National Academies of Sciences, Engineering and Medicine on how to increase the research involvement of under-represented groups.

Dr. Bothwell said, “The problem with industry funded research is that ... it’s an inevitable conflict of interest that exists. They want the research to show that their products work. And older populations ... have a lot more complications, which leads to potentially less favorable results.”

The MD Anderson findings were published in JAMA Oncology. “That was the starting point in our journey,” said Dr. Ludmir. For the next 3 years, the researchers mined their painstakingly constructed database to understand what was preventing greater numbers of older patients from enrollment in cancer trials.

Meanwhile, answers were coming from elsewhere. In parallel with the work at MD Anderson, a team in California led by Mina Sedrak, MD, a medical oncologist at the City of Hope National Medical Center, had also started investigating age disparities in clinical trials.

Sedrak_Mina_CA_web.jpg

Dr. Sedrak, who also serves as deputy director of Clinical Trials at the Center for Cancer and Aging, said he had become increasingly concerned that he did not have adequate information on new cancer therapies for his older patients.

“I was caring for a large number of people who were ... older adults,” said Dr. Sedrak, “But the data that was being used to get the standard-of-care treatment for cancer did not include older adults. And so there was this lack of applicability.”

He summed up the challenges in a 2021 review paper: “Most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients.”

By 2030, it is estimated that 70% of all new cancer diagnoses will be in patients 65 years old and older. By contrast, patients over age 65 still account for only 40% of patients in cancer trials registered with the FDA (2015 figures) and older adults make up only 44% of participants in practice-changing cancer trials, according to a 2022 study.

So what is going on? Are studies specifically designed to squeeze out older patients?

Surprisingly, patients are not being kept out of trials by formal age limits, according to Dr. Ludmir. His team found that only 10% of phase 3 trials over the past 30 years had an upper limit for age, and age restrictions have been dropping by 1% a year. (For example, 16% of trials that enrolled in 2002-2005 had an upper age limit, compared with just 8% of trials that started in 2010-2014.)

Dr. Sedrak’s team found that “clinician bias” may be a factor, a situation in which trial investigators – particularly academic oncologists – are subconsciously picking younger, healthier patients for trials and excluding older, sicker patients to protect them from drug toxicities.

Dr. Ludmir said this was understandable, especially in the case of industry-driven trials, which tend to have demanding endpoints and “an overall posture of more treatment aggressiveness.”

“These are typically not trials where they’re saying, `Hey, if we add acupuncture ... are we going to see improved patient reported outcomes?’” Dr. Ludmir explained. “You’re asking ... I’ve got this cocktail of two pretty rough chemos: I want to see what happens if I add an immunotherapy to that. If I’m the clinician in clinic, I might reasonably, subconsciously, say, is the 75-year-old really who I want on this?”

What about patient bias? Perhaps fewer older patients wish to join clinical trials?

Not so, at least not at community cancer centers, said Dr. Sedrak. His team’s analysis of the National Cancer Institute Community Oncology Research Program database for 2016-2019 revealed that older patients were just as keen as the younger patients to participate in trials (68% of patients aged 50-69 years and 65% of patients 70+; P = .28).

However, drug companies may be excluding older patients by more subtle means. One-fifth of patients over 65 have had a prior cancer. Dr. Ludmir and coauthor Roshal Patel, MD, used their hand-coded www.clinicaltrials.gov database to look at prior malignancy exclusion criteria (PMEC). The analysis found “pervasive utilization” of PMEC in phase 3 trials, cropping up in 41% of studies over the past 30 years.

PMEC was significantly associated with age disparities and was significantly more common in industry-funded trials.

When asked whether PMEC are “age restriction by stealth” on the part of drug companies, Dr. Ludmir was reluctant to assign blame, but stood by his data: “The wider you restrict people in terms of having a prior cancer, the wider the age disparities in the subsequent studies, which to me is about as strong, in terms of causal understanding of these phenomena, as you can reasonably get at this level.”

In March the FDA released a guidance document titled Inclusion of Older Adults in Cancer Clinical Trials. However, its recommendations are “nonbinding” and “do not have the force and effect of law.”

To fix the issues, said Dr. Sedrak, the FDA must be given teeth.

“Okay, you write guidelines,” he said. “But if you don’t actually hold people accountable to following the guidelines, how are we going to implement and make sure that we’re transforming policy into action?”

Dr. Bothwell of Yale’s School of Public Health agreed. “Accountability has been the weakest link for decades now.”

She concluded, “In medicine there’s a tendency to believe that a therapy, because it exists and it has been tested and it’s shown some efficacy, it’s useful. But we don’t know the answer to that question unless we have statistically valid research in the population that we’re using it in.”

Dr. Bothwell and Dr. Ludmir report no conflicts of interest. In his publications, Dr. Sedrak reports industry grants from Seattle Genetics, Eli Lilly, Novartis, and Pfizer Foundation.
 

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Approximately one-fifth of cervical cancer cases are diagnosed in women aged 65 years or older, and most of the cases are late-stage disease associated with poor survival rates. The new finding calls into question yet again the many national screening guidelines that advise physicians to halt cervical screening at age 65.

The findings emerged from an analysis of the California Cancer Registry for 2009-2018. The authors, from the University of California, Davis, who manage the registry on behalf of the state, found that 17% of women diagnosed with a first primary cancer were aged 65 years or older.

Up to 71% of these older women had late-stage disease vs. 34%-to 59% of women aged 21-64.

The team also found that older patients, even those with early disease, had much poorer survival after they were diagnosed with cervical cancer than their younger counterparts. For example, patients aged between 65 and 69 with stage I cervical cancer had a 5-year relative survival – that is, survival adjusted for noncancer causes of death – of 82%. By contrast, 94% of women aged 20-39 survived for at least 5 years.

The study was published on January 9 in Cancer Epidemiology, Biomarkers & Prevention.

These new data echo similar findings from other recent cervical cancer studies out of California, Massachusetts, Ohio, and nationally. Those studies show that, in comparison with younger patients, rates of late-stage disease are higher and survival is poorer among women aged 65 and older.

Even so, a coauthor of the present study, Frances Maguire, PhD, who is an epidemiologist at the University of California, Davis, said she and her colleagues were surprised by what they found.

“There are a lot of women in this older-age category who are being diagnosed, and they’re being diagnosed later stage and their survival is worse,” Dr. Maguire said. “That was surprising to all of us,” given that the current recommendations are to stop screening once women reach the age of 65, and yet this age group is “doing quite poorly.”

The American Cancer Society, the U.S. Preventive Services Task Force, and the American College of Obstetricians and Gynecologists all recommend that cervical screening stop at aged 65 for patients with “adequate prior screening.”

Adequate screening is defined as having three consecutive normal Pap tests or two consecutive negative human papillomavirus tests or two consecutive negative cotests within the prior 10 years, with the most recent screening within 5 years and having no precancerous lesions in the past 25 years.

However, as many as 23% of women aged 60-64 report that their last Pap test was administered more than 5 years ago, according to a recent study by Alex Francoeur, MD, and colleagues at the University of California, Los Angeles.

When asked to comment on the new article, Dr. Francoeur said, “There is literature that increasing comorbidities and visits to the doctor [with age] decrease the likelihood of getting a Pap test, which is concerning, as these may be the highest-risk women.”

Said study author Dr. Maguire, “It could be that [the guidelines] are perfectly fine if women were properly screened before they hit 65, so that’s one of our big questions. Perhaps this group are not properly screened before age 65, and then they hit 65, they don’t screen, and this is the result we’re seeing.”

The situation is compounded by the lack of continuity in care at this crucial juncture, said Alexander Olawaiye, MD, a professor in the division of gynecologic oncology at the University of Pittsburgh, who was also approached for comment.

At age 65, many women retire, move across the country, or access new health care providers through Medicare, which kicks in at age 65, so the woman’s new physician doesn’t have access to her screening history, he commented.

This means that a physician needs to rely on the patient’s memory.

This is unrealistic, said Dr. Olawaiye: “Let’s forget about the 65-year-old women for now. Let’s talk about young women with sharp minds. Half of these young adults cannot even remember correctly their last monthly period. And these are the people you want to recollect accurately [at age 65] the number of tests they’ve had over 10 years and the results of those tests? Are you kidding me?” said Dr. Olawaiye. “Is that the kind of verification that you rely on?”

Dr. Olawaiye has consistently advocated for scrapping the 65+ screening moratorium in past and current versions of the cervical screening guidelines. He is puzzled by the national unwillingness to do so and rejects the economic argument, pointing out that a handful of extra tests is a lot cheaper than caring for a patient with advanced cervical cancer.

“Most American women will die around 84-85 years of age,” Dr. Olawaiye commented. “So between 65 and 85, you will need five screens, maybe four. What are you saving by not doing that?”

Dr. Maguire, Dr. Francoeur, and Dr. Olawaiye have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately one-fifth of cervical cancer cases are diagnosed in women aged 65 years or older, and most of the cases are late-stage disease associated with poor survival rates. The new finding calls into question yet again the many national screening guidelines that advise physicians to halt cervical screening at age 65.

The findings emerged from an analysis of the California Cancer Registry for 2009-2018. The authors, from the University of California, Davis, who manage the registry on behalf of the state, found that 17% of women diagnosed with a first primary cancer were aged 65 years or older.

Up to 71% of these older women had late-stage disease vs. 34%-to 59% of women aged 21-64.

The team also found that older patients, even those with early disease, had much poorer survival after they were diagnosed with cervical cancer than their younger counterparts. For example, patients aged between 65 and 69 with stage I cervical cancer had a 5-year relative survival – that is, survival adjusted for noncancer causes of death – of 82%. By contrast, 94% of women aged 20-39 survived for at least 5 years.

The study was published on January 9 in Cancer Epidemiology, Biomarkers & Prevention.

These new data echo similar findings from other recent cervical cancer studies out of California, Massachusetts, Ohio, and nationally. Those studies show that, in comparison with younger patients, rates of late-stage disease are higher and survival is poorer among women aged 65 and older.

Even so, a coauthor of the present study, Frances Maguire, PhD, who is an epidemiologist at the University of California, Davis, said she and her colleagues were surprised by what they found.

“There are a lot of women in this older-age category who are being diagnosed, and they’re being diagnosed later stage and their survival is worse,” Dr. Maguire said. “That was surprising to all of us,” given that the current recommendations are to stop screening once women reach the age of 65, and yet this age group is “doing quite poorly.”

The American Cancer Society, the U.S. Preventive Services Task Force, and the American College of Obstetricians and Gynecologists all recommend that cervical screening stop at aged 65 for patients with “adequate prior screening.”

Adequate screening is defined as having three consecutive normal Pap tests or two consecutive negative human papillomavirus tests or two consecutive negative cotests within the prior 10 years, with the most recent screening within 5 years and having no precancerous lesions in the past 25 years.

However, as many as 23% of women aged 60-64 report that their last Pap test was administered more than 5 years ago, according to a recent study by Alex Francoeur, MD, and colleagues at the University of California, Los Angeles.

When asked to comment on the new article, Dr. Francoeur said, “There is literature that increasing comorbidities and visits to the doctor [with age] decrease the likelihood of getting a Pap test, which is concerning, as these may be the highest-risk women.”

Said study author Dr. Maguire, “It could be that [the guidelines] are perfectly fine if women were properly screened before they hit 65, so that’s one of our big questions. Perhaps this group are not properly screened before age 65, and then they hit 65, they don’t screen, and this is the result we’re seeing.”

The situation is compounded by the lack of continuity in care at this crucial juncture, said Alexander Olawaiye, MD, a professor in the division of gynecologic oncology at the University of Pittsburgh, who was also approached for comment.

At age 65, many women retire, move across the country, or access new health care providers through Medicare, which kicks in at age 65, so the woman’s new physician doesn’t have access to her screening history, he commented.

This means that a physician needs to rely on the patient’s memory.

This is unrealistic, said Dr. Olawaiye: “Let’s forget about the 65-year-old women for now. Let’s talk about young women with sharp minds. Half of these young adults cannot even remember correctly their last monthly period. And these are the people you want to recollect accurately [at age 65] the number of tests they’ve had over 10 years and the results of those tests? Are you kidding me?” said Dr. Olawaiye. “Is that the kind of verification that you rely on?”

Dr. Olawaiye has consistently advocated for scrapping the 65+ screening moratorium in past and current versions of the cervical screening guidelines. He is puzzled by the national unwillingness to do so and rejects the economic argument, pointing out that a handful of extra tests is a lot cheaper than caring for a patient with advanced cervical cancer.

“Most American women will die around 84-85 years of age,” Dr. Olawaiye commented. “So between 65 and 85, you will need five screens, maybe four. What are you saving by not doing that?”

Dr. Maguire, Dr. Francoeur, and Dr. Olawaiye have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately one-fifth of cervical cancer cases are diagnosed in women aged 65 years or older, and most of the cases are late-stage disease associated with poor survival rates. The new finding calls into question yet again the many national screening guidelines that advise physicians to halt cervical screening at age 65.

The findings emerged from an analysis of the California Cancer Registry for 2009-2018. The authors, from the University of California, Davis, who manage the registry on behalf of the state, found that 17% of women diagnosed with a first primary cancer were aged 65 years or older.

Up to 71% of these older women had late-stage disease vs. 34%-to 59% of women aged 21-64.

The team also found that older patients, even those with early disease, had much poorer survival after they were diagnosed with cervical cancer than their younger counterparts. For example, patients aged between 65 and 69 with stage I cervical cancer had a 5-year relative survival – that is, survival adjusted for noncancer causes of death – of 82%. By contrast, 94% of women aged 20-39 survived for at least 5 years.

The study was published on January 9 in Cancer Epidemiology, Biomarkers & Prevention.

These new data echo similar findings from other recent cervical cancer studies out of California, Massachusetts, Ohio, and nationally. Those studies show that, in comparison with younger patients, rates of late-stage disease are higher and survival is poorer among women aged 65 and older.

Even so, a coauthor of the present study, Frances Maguire, PhD, who is an epidemiologist at the University of California, Davis, said she and her colleagues were surprised by what they found.

“There are a lot of women in this older-age category who are being diagnosed, and they’re being diagnosed later stage and their survival is worse,” Dr. Maguire said. “That was surprising to all of us,” given that the current recommendations are to stop screening once women reach the age of 65, and yet this age group is “doing quite poorly.”

The American Cancer Society, the U.S. Preventive Services Task Force, and the American College of Obstetricians and Gynecologists all recommend that cervical screening stop at aged 65 for patients with “adequate prior screening.”

Adequate screening is defined as having three consecutive normal Pap tests or two consecutive negative human papillomavirus tests or two consecutive negative cotests within the prior 10 years, with the most recent screening within 5 years and having no precancerous lesions in the past 25 years.

However, as many as 23% of women aged 60-64 report that their last Pap test was administered more than 5 years ago, according to a recent study by Alex Francoeur, MD, and colleagues at the University of California, Los Angeles.

When asked to comment on the new article, Dr. Francoeur said, “There is literature that increasing comorbidities and visits to the doctor [with age] decrease the likelihood of getting a Pap test, which is concerning, as these may be the highest-risk women.”

Said study author Dr. Maguire, “It could be that [the guidelines] are perfectly fine if women were properly screened before they hit 65, so that’s one of our big questions. Perhaps this group are not properly screened before age 65, and then they hit 65, they don’t screen, and this is the result we’re seeing.”

The situation is compounded by the lack of continuity in care at this crucial juncture, said Alexander Olawaiye, MD, a professor in the division of gynecologic oncology at the University of Pittsburgh, who was also approached for comment.

At age 65, many women retire, move across the country, or access new health care providers through Medicare, which kicks in at age 65, so the woman’s new physician doesn’t have access to her screening history, he commented.

This means that a physician needs to rely on the patient’s memory.

This is unrealistic, said Dr. Olawaiye: “Let’s forget about the 65-year-old women for now. Let’s talk about young women with sharp minds. Half of these young adults cannot even remember correctly their last monthly period. And these are the people you want to recollect accurately [at age 65] the number of tests they’ve had over 10 years and the results of those tests? Are you kidding me?” said Dr. Olawaiye. “Is that the kind of verification that you rely on?”

Dr. Olawaiye has consistently advocated for scrapping the 65+ screening moratorium in past and current versions of the cervical screening guidelines. He is puzzled by the national unwillingness to do so and rejects the economic argument, pointing out that a handful of extra tests is a lot cheaper than caring for a patient with advanced cervical cancer.

“Most American women will die around 84-85 years of age,” Dr. Olawaiye commented. “So between 65 and 85, you will need five screens, maybe four. What are you saving by not doing that?”

Dr. Maguire, Dr. Francoeur, and Dr. Olawaiye have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Following “unprecedented” results in a phase 1/2 study, teclistamab (Tecvayli, Janssen Biotech) received accelerated approval from the Food and Drug Administration for adults with relapsed/refractory multiple myeloma who had received at least four lines of therapy. Typically, patients in this situation have just a few weeks to live. The nod from the FDA on Oct. 25 for teclistamab, the first bispecific B-cell maturation antigen–directed CD3 T-cell engager to be approved, was based on data from a phase 1/2 study called MagesTEC-1 (NCT03145181; NCT04557098). Patients in the study showed an overall response rate of 61.8%, and 26.7% of people in the study had no detectable disease.

This is “unprecedented” said Nikhil Munshi, MD, professor of medicine at Harvard Medical School, Boston, who was not involved with the study. “Pomalidomide got approved with 30% response rate, carfilzomib got approved with 29% response rate, selinexor got approved with 31% response rate and so on and on. ... So here is teclistamab with [this] response rate in patients having five, six lines of treatment. ...[It’s] going to be so much in demand because it’s a great drug.”

The first cut of the data appeared in the New England Journal of Medicine.

At the 6-month mark, 90.6% of patients who responded had no progression of their disease, and at 9 months, 66.5% of patients were still holding steady.

Senior investigator in the trial, Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York, said: “What was most striking was the high response rates and the durability of response.”

Dr. Usmani said ease of administration was the other aspect of teclistamab that impressed him. The drug is given by subcutaneous injection weekly after a short ramp-up period.

He contrasted this regimen with that of chimeric antigen receptor (CAR) T-cell therapy, the only alternative with similar efficacy in such sick patients: “I can prescribe [teclistamab] today, and my patient gets it tomorrow,” Dr. Usmani said. “With CAR T, I prescribe today and it will take 4-6 weeks for us to collect T cells and another 6-7 weeks for the product to come back.” Dr. Usmani said many patients die before CAR T reaches them.

Community oncology will benefit greatly from teclistamab, especially patients for whom CAR T isn’t feasible, said Kashyap Patel, MD, president of the Community Oncology Alliance. “My patients are most of them underserved minority-class populations with myeloma, and they cannot travel many miles to go to a CAR T center. With sub[cutaneous] injection, the patient can have [teclistamab] administered in their doctor’s office and continue to live their normal life.”

However, how should the wider oncology community make sense of a drug approval based solely on response in a single-arm, phase 1/2 study, with no survival data?

Dr. Patel said, “Phase 1 plus phase 2 data is probably a little bit quick, but time will tell eventually.” He cited melflufen as a cautionary tale: a product given accelerated approval for multiple myeloma, then withdrawn when new data showed that it increased the risk of death.

When Dr. Munshi was asked about trial design for accelerated approvals, he responded, “you are touching a topic very close to my heart, a topic of great significance currently.”

He went on to say that overall survival (OS) is no longer a viable trial endpoint in diseases like multiple myeloma for several reasons. Most significantly, he noted: “Survival has gone up to 10 or 15 years [so] today, if you randomize between one [drug] versus another, there are going to be seven or eight more treatments before the patient dies.”

Similarly, progression-free survival (PFS) in multiple myeloma is now as much as 5 years, Dr. Munshi said. “Do we want a patient to wait 5 years to get a very good new drug?”

For these reasons and others, Dr, Munshi observed, myeloma researchers are increasingly relying on a surrogate called “negative minimal residual disease” (negative MRD) – in other words, a situation in which myeloma cells can no longer be detected in the bone marrow. MRD is hunted out using next-generation flow or next-generation sequencing of myeloma-cell DNA from bone-marrow aspirate to levels as low as 1 in 100,000 or 1,000,000 cells.

In 2020, Dr. Munshi and colleagues published a large meta-analysis showing that a negative MRD in a patient with multiple myeloma was significantly prognostic for both progression-free survival (hazard ratio, 0.33; P < .001) and overall survival (HR, 0.45; P < .001). The team concluded: “MRD can fulfill all the prerequisites to be a clinically valid surrogate biomarker for PFS and OS in [multiple myeloma].”

In MajesTEC-1 overall, 26.7% of patients on teclistamab had no signs of residual disease at a threshold of 1 in 100,000. Among patients who showed a “complete response” by International Myeloma Working Group criteria, 46% had no residual disease.

Dr. Munshi stressed that such patients are not necessarily “cured.” It will take a few more years to prove that. He noted: “Simply, physiologically, [negative MRD] means that if a patient has one [myeloma] cell in a million, that cell is going to take a much longer time to grow up to be myeloma.”

On Nov. 8 and 9, the FDA and the International Myeloma Society held a workshop to discuss the vexed question of surrogate endpoints and single-arm studies for drug approvals entitled the “Future of Drug Development in Multiple Myeloma.” Dr. Munshi was cochair.

A panelist at the meeting who was a senior investigator in the MajesTEC-1 trial, Ajai Chari, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, summed up the dilemma: “No one disagrees that randomized studies are the best way of doing things. The question is, if you’re a patient who’s exhausted all available therapies, do you have that time to wait? ... The role of accelerated approval is to get the drug to the patient faster. But what does it not pick up? How do we make these accelerated approvals more meaningful and not have to retract for safety?”

Jonathon Vallejo, also on the panel, agreed that safety was the key worry. The ideal scenario for accelerated approval would be a drug that was better than available therapy, and “in some sense, it’s much safer.” However, such situations are rare.

“Most of the time, we don’t have these products that come in that have no toxicity signals,” he said. “So one thing we have to think carefully about in the single-arm trial setting is, what are the toxicities? How do they stack up?”

Dr. Chari said that, for his part, he wanted to see more transparency around “cause of death” in all studies that lead to accelerated approvals. He said he was “tired” of seeing a death labeled as “not attributed” to the drug by the investigator or the drug company.

“Let me decide. Show me the deaths, and show me the myeloma status at that point,” Dr. Chari said. “That’s a signal – if you’re a responding patient and dying, then the FDA should be a little bit more cautious.”

The FDA has added a boxed warning to the teclistamab product information concerning cytokine-release syndrome and neurologic toxicity.

Cytokine-release syndrome, the most common side effect overall, showed up in 72% of patients, typically 2 days after the first step-up dose.

Neurologic toxicity occurred in 57% of patients, including headache (25%), motor dysfunction (16%), sensory neuropathy (15%) and encephalopathy (13%). About 6%of patients developed a serious, life-threatening neurologic condition called immune effector cell–associated neurotoxicity syndrome.

Overall, serious adverse reactions occurred in 54% of participants in MajesTEC-1, and 5% of people in the trial died from adverse reactions during the study, most commonly infections.

Because of its safety profile, teclistamab is available only through a restricted program called TECVAYLI Risk Evaluation and Mitigation Strategy.

The continued approval of teclistamab for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

To that end, eight more studies of teclistamab are underway, aiming for approximately 1,300 multiple myeloma patients around the world. Three of these trials are in newly diagnosed patients. Four more studies are planned to come online in the next 3 months, raising the final tally of patients testing out teclistamab to approximately 4,700. The trials will look at teclistamab in sequence or in combination with standards such as bortezomib and pomalidomide. All studies are open label.

Dr. Patel believes that, until these trials say otherwise, the benefits of teclistamab outweigh the risks. “I’m very happy we have one more option in this space, particularly the fourth or fifth line for patients who want to continue to fight the disease,” Dr. Patel concluded.

Dr. Munshi disclosed advisory board/consultant work for Adaptive, Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Karyopharm, Legend, Millennium, Novartis, Oncopep, and Pfizer and is the scientific founder of Oncopep and DCT. The 2020 meta-analysis by Dr. Munshi and colleagues was funded by Janssen-Cilag. Dr. Patel declared funding from Janssen for a diversity-equity initiative and membership of the South Carolina Medicaid P & T Committee. Dr. Usmani declared conflicts of interest with Amgen, BMS/Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, Abbvie, Genentech, Gilead, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, and TeneoBio.

Following “unprecedented” results in a phase 1/2 study, teclistamab (Tecvayli, Janssen Biotech) received accelerated approval from the Food and Drug Administration for adults with relapsed/refractory multiple myeloma who had received at least four lines of therapy. Typically, patients in this situation have just a few weeks to live. The nod from the FDA on Oct. 25 for teclistamab, the first bispecific B-cell maturation antigen–directed CD3 T-cell engager to be approved, was based on data from a phase 1/2 study called MagesTEC-1 (NCT03145181; NCT04557098). Patients in the study showed an overall response rate of 61.8%, and 26.7% of people in the study had no detectable disease.

This is “unprecedented” said Nikhil Munshi, MD, professor of medicine at Harvard Medical School, Boston, who was not involved with the study. “Pomalidomide got approved with 30% response rate, carfilzomib got approved with 29% response rate, selinexor got approved with 31% response rate and so on and on. ... So here is teclistamab with [this] response rate in patients having five, six lines of treatment. ...[It’s] going to be so much in demand because it’s a great drug.”

The first cut of the data appeared in the New England Journal of Medicine.

At the 6-month mark, 90.6% of patients who responded had no progression of their disease, and at 9 months, 66.5% of patients were still holding steady.

Senior investigator in the trial, Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York, said: “What was most striking was the high response rates and the durability of response.”

Dr. Usmani said ease of administration was the other aspect of teclistamab that impressed him. The drug is given by subcutaneous injection weekly after a short ramp-up period.

He contrasted this regimen with that of chimeric antigen receptor (CAR) T-cell therapy, the only alternative with similar efficacy in such sick patients: “I can prescribe [teclistamab] today, and my patient gets it tomorrow,” Dr. Usmani said. “With CAR T, I prescribe today and it will take 4-6 weeks for us to collect T cells and another 6-7 weeks for the product to come back.” Dr. Usmani said many patients die before CAR T reaches them.

Community oncology will benefit greatly from teclistamab, especially patients for whom CAR T isn’t feasible, said Kashyap Patel, MD, president of the Community Oncology Alliance. “My patients are most of them underserved minority-class populations with myeloma, and they cannot travel many miles to go to a CAR T center. With sub[cutaneous] injection, the patient can have [teclistamab] administered in their doctor’s office and continue to live their normal life.”

However, how should the wider oncology community make sense of a drug approval based solely on response in a single-arm, phase 1/2 study, with no survival data?

Dr. Patel said, “Phase 1 plus phase 2 data is probably a little bit quick, but time will tell eventually.” He cited melflufen as a cautionary tale: a product given accelerated approval for multiple myeloma, then withdrawn when new data showed that it increased the risk of death.

When Dr. Munshi was asked about trial design for accelerated approvals, he responded, “you are touching a topic very close to my heart, a topic of great significance currently.”

He went on to say that overall survival (OS) is no longer a viable trial endpoint in diseases like multiple myeloma for several reasons. Most significantly, he noted: “Survival has gone up to 10 or 15 years [so] today, if you randomize between one [drug] versus another, there are going to be seven or eight more treatments before the patient dies.”

Similarly, progression-free survival (PFS) in multiple myeloma is now as much as 5 years, Dr. Munshi said. “Do we want a patient to wait 5 years to get a very good new drug?”

For these reasons and others, Dr, Munshi observed, myeloma researchers are increasingly relying on a surrogate called “negative minimal residual disease” (negative MRD) – in other words, a situation in which myeloma cells can no longer be detected in the bone marrow. MRD is hunted out using next-generation flow or next-generation sequencing of myeloma-cell DNA from bone-marrow aspirate to levels as low as 1 in 100,000 or 1,000,000 cells.

In 2020, Dr. Munshi and colleagues published a large meta-analysis showing that a negative MRD in a patient with multiple myeloma was significantly prognostic for both progression-free survival (hazard ratio, 0.33; P < .001) and overall survival (HR, 0.45; P < .001). The team concluded: “MRD can fulfill all the prerequisites to be a clinically valid surrogate biomarker for PFS and OS in [multiple myeloma].”

In MajesTEC-1 overall, 26.7% of patients on teclistamab had no signs of residual disease at a threshold of 1 in 100,000. Among patients who showed a “complete response” by International Myeloma Working Group criteria, 46% had no residual disease.

Dr. Munshi stressed that such patients are not necessarily “cured.” It will take a few more years to prove that. He noted: “Simply, physiologically, [negative MRD] means that if a patient has one [myeloma] cell in a million, that cell is going to take a much longer time to grow up to be myeloma.”

On Nov. 8 and 9, the FDA and the International Myeloma Society held a workshop to discuss the vexed question of surrogate endpoints and single-arm studies for drug approvals entitled the “Future of Drug Development in Multiple Myeloma.” Dr. Munshi was cochair.

A panelist at the meeting who was a senior investigator in the MajesTEC-1 trial, Ajai Chari, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, summed up the dilemma: “No one disagrees that randomized studies are the best way of doing things. The question is, if you’re a patient who’s exhausted all available therapies, do you have that time to wait? ... The role of accelerated approval is to get the drug to the patient faster. But what does it not pick up? How do we make these accelerated approvals more meaningful and not have to retract for safety?”

Jonathon Vallejo, also on the panel, agreed that safety was the key worry. The ideal scenario for accelerated approval would be a drug that was better than available therapy, and “in some sense, it’s much safer.” However, such situations are rare.

“Most of the time, we don’t have these products that come in that have no toxicity signals,” he said. “So one thing we have to think carefully about in the single-arm trial setting is, what are the toxicities? How do they stack up?”

Dr. Chari said that, for his part, he wanted to see more transparency around “cause of death” in all studies that lead to accelerated approvals. He said he was “tired” of seeing a death labeled as “not attributed” to the drug by the investigator or the drug company.

“Let me decide. Show me the deaths, and show me the myeloma status at that point,” Dr. Chari said. “That’s a signal – if you’re a responding patient and dying, then the FDA should be a little bit more cautious.”

The FDA has added a boxed warning to the teclistamab product information concerning cytokine-release syndrome and neurologic toxicity.

Cytokine-release syndrome, the most common side effect overall, showed up in 72% of patients, typically 2 days after the first step-up dose.

Neurologic toxicity occurred in 57% of patients, including headache (25%), motor dysfunction (16%), sensory neuropathy (15%) and encephalopathy (13%). About 6%of patients developed a serious, life-threatening neurologic condition called immune effector cell–associated neurotoxicity syndrome.

Overall, serious adverse reactions occurred in 54% of participants in MajesTEC-1, and 5% of people in the trial died from adverse reactions during the study, most commonly infections.

Because of its safety profile, teclistamab is available only through a restricted program called TECVAYLI Risk Evaluation and Mitigation Strategy.

The continued approval of teclistamab for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

To that end, eight more studies of teclistamab are underway, aiming for approximately 1,300 multiple myeloma patients around the world. Three of these trials are in newly diagnosed patients. Four more studies are planned to come online in the next 3 months, raising the final tally of patients testing out teclistamab to approximately 4,700. The trials will look at teclistamab in sequence or in combination with standards such as bortezomib and pomalidomide. All studies are open label.

Dr. Patel believes that, until these trials say otherwise, the benefits of teclistamab outweigh the risks. “I’m very happy we have one more option in this space, particularly the fourth or fifth line for patients who want to continue to fight the disease,” Dr. Patel concluded.

Dr. Munshi disclosed advisory board/consultant work for Adaptive, Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Karyopharm, Legend, Millennium, Novartis, Oncopep, and Pfizer and is the scientific founder of Oncopep and DCT. The 2020 meta-analysis by Dr. Munshi and colleagues was funded by Janssen-Cilag. Dr. Patel declared funding from Janssen for a diversity-equity initiative and membership of the South Carolina Medicaid P & T Committee. Dr. Usmani declared conflicts of interest with Amgen, BMS/Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, Abbvie, Genentech, Gilead, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, and TeneoBio.

Following “unprecedented” results in a phase 1/2 study, teclistamab (Tecvayli, Janssen Biotech) received accelerated approval from the Food and Drug Administration for adults with relapsed/refractory multiple myeloma who had received at least four lines of therapy. Typically, patients in this situation have just a few weeks to live. The nod from the FDA on Oct. 25 for teclistamab, the first bispecific B-cell maturation antigen–directed CD3 T-cell engager to be approved, was based on data from a phase 1/2 study called MagesTEC-1 (NCT03145181; NCT04557098). Patients in the study showed an overall response rate of 61.8%, and 26.7% of people in the study had no detectable disease.

This is “unprecedented” said Nikhil Munshi, MD, professor of medicine at Harvard Medical School, Boston, who was not involved with the study. “Pomalidomide got approved with 30% response rate, carfilzomib got approved with 29% response rate, selinexor got approved with 31% response rate and so on and on. ... So here is teclistamab with [this] response rate in patients having five, six lines of treatment. ...[It’s] going to be so much in demand because it’s a great drug.”

The first cut of the data appeared in the New England Journal of Medicine.

At the 6-month mark, 90.6% of patients who responded had no progression of their disease, and at 9 months, 66.5% of patients were still holding steady.

Senior investigator in the trial, Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York, said: “What was most striking was the high response rates and the durability of response.”

Dr. Usmani said ease of administration was the other aspect of teclistamab that impressed him. The drug is given by subcutaneous injection weekly after a short ramp-up period.

He contrasted this regimen with that of chimeric antigen receptor (CAR) T-cell therapy, the only alternative with similar efficacy in such sick patients: “I can prescribe [teclistamab] today, and my patient gets it tomorrow,” Dr. Usmani said. “With CAR T, I prescribe today and it will take 4-6 weeks for us to collect T cells and another 6-7 weeks for the product to come back.” Dr. Usmani said many patients die before CAR T reaches them.

Community oncology will benefit greatly from teclistamab, especially patients for whom CAR T isn’t feasible, said Kashyap Patel, MD, president of the Community Oncology Alliance. “My patients are most of them underserved minority-class populations with myeloma, and they cannot travel many miles to go to a CAR T center. With sub[cutaneous] injection, the patient can have [teclistamab] administered in their doctor’s office and continue to live their normal life.”

However, how should the wider oncology community make sense of a drug approval based solely on response in a single-arm, phase 1/2 study, with no survival data?

Dr. Patel said, “Phase 1 plus phase 2 data is probably a little bit quick, but time will tell eventually.” He cited melflufen as a cautionary tale: a product given accelerated approval for multiple myeloma, then withdrawn when new data showed that it increased the risk of death.

When Dr. Munshi was asked about trial design for accelerated approvals, he responded, “you are touching a topic very close to my heart, a topic of great significance currently.”

He went on to say that overall survival (OS) is no longer a viable trial endpoint in diseases like multiple myeloma for several reasons. Most significantly, he noted: “Survival has gone up to 10 or 15 years [so] today, if you randomize between one [drug] versus another, there are going to be seven or eight more treatments before the patient dies.”

Similarly, progression-free survival (PFS) in multiple myeloma is now as much as 5 years, Dr. Munshi said. “Do we want a patient to wait 5 years to get a very good new drug?”

For these reasons and others, Dr, Munshi observed, myeloma researchers are increasingly relying on a surrogate called “negative minimal residual disease” (negative MRD) – in other words, a situation in which myeloma cells can no longer be detected in the bone marrow. MRD is hunted out using next-generation flow or next-generation sequencing of myeloma-cell DNA from bone-marrow aspirate to levels as low as 1 in 100,000 or 1,000,000 cells.

In 2020, Dr. Munshi and colleagues published a large meta-analysis showing that a negative MRD in a patient with multiple myeloma was significantly prognostic for both progression-free survival (hazard ratio, 0.33; P < .001) and overall survival (HR, 0.45; P < .001). The team concluded: “MRD can fulfill all the prerequisites to be a clinically valid surrogate biomarker for PFS and OS in [multiple myeloma].”

In MajesTEC-1 overall, 26.7% of patients on teclistamab had no signs of residual disease at a threshold of 1 in 100,000. Among patients who showed a “complete response” by International Myeloma Working Group criteria, 46% had no residual disease.

Dr. Munshi stressed that such patients are not necessarily “cured.” It will take a few more years to prove that. He noted: “Simply, physiologically, [negative MRD] means that if a patient has one [myeloma] cell in a million, that cell is going to take a much longer time to grow up to be myeloma.”

On Nov. 8 and 9, the FDA and the International Myeloma Society held a workshop to discuss the vexed question of surrogate endpoints and single-arm studies for drug approvals entitled the “Future of Drug Development in Multiple Myeloma.” Dr. Munshi was cochair.

A panelist at the meeting who was a senior investigator in the MajesTEC-1 trial, Ajai Chari, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, summed up the dilemma: “No one disagrees that randomized studies are the best way of doing things. The question is, if you’re a patient who’s exhausted all available therapies, do you have that time to wait? ... The role of accelerated approval is to get the drug to the patient faster. But what does it not pick up? How do we make these accelerated approvals more meaningful and not have to retract for safety?”

Jonathon Vallejo, also on the panel, agreed that safety was the key worry. The ideal scenario for accelerated approval would be a drug that was better than available therapy, and “in some sense, it’s much safer.” However, such situations are rare.

“Most of the time, we don’t have these products that come in that have no toxicity signals,” he said. “So one thing we have to think carefully about in the single-arm trial setting is, what are the toxicities? How do they stack up?”

Dr. Chari said that, for his part, he wanted to see more transparency around “cause of death” in all studies that lead to accelerated approvals. He said he was “tired” of seeing a death labeled as “not attributed” to the drug by the investigator or the drug company.

“Let me decide. Show me the deaths, and show me the myeloma status at that point,” Dr. Chari said. “That’s a signal – if you’re a responding patient and dying, then the FDA should be a little bit more cautious.”

The FDA has added a boxed warning to the teclistamab product information concerning cytokine-release syndrome and neurologic toxicity.

Cytokine-release syndrome, the most common side effect overall, showed up in 72% of patients, typically 2 days after the first step-up dose.

Neurologic toxicity occurred in 57% of patients, including headache (25%), motor dysfunction (16%), sensory neuropathy (15%) and encephalopathy (13%). About 6%of patients developed a serious, life-threatening neurologic condition called immune effector cell–associated neurotoxicity syndrome.

Overall, serious adverse reactions occurred in 54% of participants in MajesTEC-1, and 5% of people in the trial died from adverse reactions during the study, most commonly infections.

Because of its safety profile, teclistamab is available only through a restricted program called TECVAYLI Risk Evaluation and Mitigation Strategy.

The continued approval of teclistamab for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

To that end, eight more studies of teclistamab are underway, aiming for approximately 1,300 multiple myeloma patients around the world. Three of these trials are in newly diagnosed patients. Four more studies are planned to come online in the next 3 months, raising the final tally of patients testing out teclistamab to approximately 4,700. The trials will look at teclistamab in sequence or in combination with standards such as bortezomib and pomalidomide. All studies are open label.

Dr. Patel believes that, until these trials say otherwise, the benefits of teclistamab outweigh the risks. “I’m very happy we have one more option in this space, particularly the fourth or fifth line for patients who want to continue to fight the disease,” Dr. Patel concluded.

Dr. Munshi disclosed advisory board/consultant work for Adaptive, Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Karyopharm, Legend, Millennium, Novartis, Oncopep, and Pfizer and is the scientific founder of Oncopep and DCT. The 2020 meta-analysis by Dr. Munshi and colleagues was funded by Janssen-Cilag. Dr. Patel declared funding from Janssen for a diversity-equity initiative and membership of the South Carolina Medicaid P & T Committee. Dr. Usmani declared conflicts of interest with Amgen, BMS/Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, Abbvie, Genentech, Gilead, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, and TeneoBio.

Kashyap Patel, MD, followed an unconventional path to becoming a nationally known oncologist. A former news photographer in his native India, Dr. Patel has practiced medicine on three continents.

In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).

Patel_Kashyap_SC_web.jpg

When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.

This news organization spoke with Dr. Patel about his unusual career path.
 

Question: Your father had a great influence on you. Can you tell us more about him?

Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.

He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.

When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
 

Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?

A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.

160078_motorcycle_web.jpg

Q: I understand that your father also triggered your interest in photography?

A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.

160078_migrant_woman_web.jpg

In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.

In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
 

160078_migrant_family_web.jpg

Q: Among all your thousands of pictures, do you have a favorite?

A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.

Q: After you finished your residency in Ahmedabad, how did you get started in oncology?

A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.

In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.

“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.

“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
 

Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?

A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.

Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?

A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.

I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.

I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.

So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.

This has now become my mission for the last quarter of my life.
 

In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.

160078_bookcover_web.jpg

Q: Why did you feel the need to write a book about dying?

A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.

Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
 

Q: What is your secret for fitting everything into your life?

A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.

Kashyap Patel, MD, followed an unconventional path to becoming a nationally known oncologist. A former news photographer in his native India, Dr. Patel has practiced medicine on three continents.

In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).

Patel_Kashyap_SC_web.jpg

When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.

This news organization spoke with Dr. Patel about his unusual career path.
 

Question: Your father had a great influence on you. Can you tell us more about him?

Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.

He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.

When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
 

Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?

A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.

160078_motorcycle_web.jpg

Q: I understand that your father also triggered your interest in photography?

A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.

160078_migrant_woman_web.jpg

In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.

In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
 

160078_migrant_family_web.jpg

Q: Among all your thousands of pictures, do you have a favorite?

A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.

Q: After you finished your residency in Ahmedabad, how did you get started in oncology?

A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.

In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.

“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.

“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
 

Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?

A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.

Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?

A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.

I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.

I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.

So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.

This has now become my mission for the last quarter of my life.
 

In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.

160078_bookcover_web.jpg

Q: Why did you feel the need to write a book about dying?

A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.

Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
 

Q: What is your secret for fitting everything into your life?

A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.

Kashyap Patel, MD, followed an unconventional path to becoming a nationally known oncologist. A former news photographer in his native India, Dr. Patel has practiced medicine on three continents.

In 2020, he published a book aimed at cancer specialists and their patients on how to die “with hope and dignity,” titled “Between Life and Death” (Penguin Random House India).

Patel_Kashyap_SC_web.jpg

When Dr. Patel, the CEO of Carolina Blood and Cancer Care Associates in Rock Hill, S.C., became president of the Washington-based Community Oncology Alliance 2 years ago, he stepped into a leadership role in community oncology. As an advocate for health care payment reform on Capitol Hill, the South Carolina legislature, and within his own practice, Dr. Patel has long worked to eliminate disparities in U.S. cancer care.

This news organization spoke with Dr. Patel about his unusual career path.
 

Question: Your father had a great influence on you. Can you tell us more about him?

Answer: My dad was a hermit and a saint. He lost his dad when he was 4 years old and moved to the big city with his cousins. When he was 9 or so, he got a message saying that his mum was very ill. So, he and his cousin raised some money, got a doctor and one of those old, rugged jeeps, and they started driving to the village, but rains had destroyed the road. So, without penicillin, his mum died of pneumonia.

He felt that roads and doctor access were the two big factors that could have saved her life. He eventually became the Superintending Engineer for four districts in Gujarat State, building roads connecting every village, but he never gave up his simplistic, minimalist life.

When I was in elementary school, every other weekend my dad would literally dump me at the Mahatma Gandhi Ashram and come back in 2 hours. So, I’m looking at Gandhi’s cabinets, his pictures, reading about his life. So, my formative years were born in that.
 

Q: I read that you were intending to become an engineer and join the space race. How did your father nudge you toward medicine?

A: When I was 9 years old, my favorite movie hero died of cancer. To comfort me, my father inserted the idea into my brain: When you grow up, you can become a doctor to cure cancer. So, when I finished high school, I was 24th in the state and had an option to go to the space school in India. On the day when I was going for the interview, I could see tears in my father’s eyes, and he said, You know what, boy? I thought you’re going to become a doctor and cure cancer. So, to honor him, I went to med school instead.

160078_motorcycle_web.jpg

Q: I understand that your father also triggered your interest in photography?

A: I started photographing Kutchi tribal people in 1977, after I bought a camera from a famous architect [Hasmukh Patel], while traveling with my dad. And then my dad bought me a motorcycle, so I started riding myself. From the time I entered med school in 1978 until I finished my residency in 1987, I made several trips following Kutchi migrant families and livestock. They leave their homeland in Kutch [district] during summer in search of grass and water to keep their livestock alive and walk across the state from the desert of Kutch all the way to central Gujarat until monsoon begins. Then they return, only to resume the journey next year. I would catch them along their journey, would talk to them, drink tea and eat millet crepes with them.

160078_migrant_woman_web.jpg

In 1984, between Dr. Patel’s medical school and residency, the Lions Club in his hometown, Ahmedabad, India, sponsored him and three buddies to document people and wildlife in Gujarat state. Traveling by motorcycle, the four friends stayed for free with local families by knocking on doors and explaining that they were medical students. Dr. Patel’s photographs were exhibited by the Lions Club of Ahmedabad and at India’s top art institution, the Lalit Kala gallery.

In the 3rd year of his internal-medicine residency in Bombay (now Mumbai), Dr. Patel approached a national newspaper, The Indian Express, for work. He was immediately sent on assignment to cover a cholera epidemic and filed his story and photographs the following day. He worked as a photojournalist and subeditor for a year.
 

160078_migrant_family_web.jpg

Q: Among all your thousands of pictures, do you have a favorite?

A: There were two photos of Kutchi people that touched me. There was one photo of a lady. All of her worldly belongings were in the picture and a smile on her face showed that we don’t need so many things to be happy. The second photo is of an elderly lady shifting her water pan on her head to a younger family member. And a little girl looks up with a look of curiosity: Will I be doing this when I grow up? We seek so much materialistic happiness. But when you look at the curiosity, smiles, and happiness [in these photos], you realize we could have a lot of happiness in minimalism, as well.

Q: After you finished your residency in Ahmedabad, how did you get started in oncology?

A: In 1986, Ahmedabad City and Gujarat State did not have structured training programs in oncology, so I went to Bombay [Mumbai], where Dr. B.C. Mehta, a true legend and pioneer in India, had started hematology-oncology training. I was a post-doc research fellow with him for a little over a year but when I started seeing patients, I had to answer to myself, Am I doing everything I can to help these people? I saw that the U.K. had one of the best training programs in hem malignancy, so I started applying. Then something happened that was almost like a miracle.

In April 1992, Dr. Patel was working at the Institute of Kidney Diseases in Ahmedabad. One afternoon, just as the clinic was closing for siesta, a family brought in a young girl. She had drug-induced thrombocytopenia and needed an immediate transfusion. The father offered to sell his wedding ring to pay Dr. Patel if he would supervise the treatment and stay by the girl’s side. Dr. Patel told the man to keep his ring, then he remained in the office with the child. At 4 p.m., the office phone rang. It was Dr. H.K. Parikh, an eminent British physician who was wintering in India and needed to make a medical appointment for his wife. On a normal day, Dr. Patel would have missed the call.

“This is how I got to meet Dr. Parikh, out of the blue,” said Dr. Patel. “His wife came to the office for 6 weeks and after 6 weeks, he said, You’re a smart guy; you should come to England. That was in April. I sent a resume and all the usual paperwork. On July 16, 1992, at 2 in the morning, I got a call from the U.K. saying, Your job is confirmed. I’m going to fax your appointment through the Royal College of Physicians, and you’re coming to Manchester to work with us. I’d been sponsored by the Overseas Doctors Training Program.

“So, it turns out that if I’d declined to see that patient and declined to stay in my clinic that afternoon, if I’d declined to see this doctor’s wife, I would never have been in the U.K. And that opened up the doors for me. I like that story because I’ve found that standing up for people who do not have a voice, who do not have hope, always leads to what is destined for me.”
 

Q: After working as a registrar in the United Kingdom 4 years, you found yourself in the United States and, once again, had to train as an internist. What was new about U.S. oncology?

A: I took 3 years to get recertified in Jamaica Hospital in Queens, then became a fellow in hematology-oncology at the Thomas Jefferson in Philadelphia. My U.K. training was all based on hematological malignancy. In the United States, I shifted into solid tumors.

Q: You have a long history of advocating for affordable oncology at the community, state, and federal level, and you recently launched a disparities initiative in your center called NOLA (No One Left Alone). What was the trigger for NOLA?

A: In the spring of 2020, when we started seeing the COVID surge and the difference in mortality rate between the multiple races, at the same time I saw the AACR [American Association for Cancer Research] 2020 disparity report showing that 34% of cancer deaths are preventable – one in three – if we took care of disparities. The same year, the Community Oncology Alliance asked me to become the president. So, I felt that there is something herding me, leading me, to this position. Eighty percent of cancer patients are treated in community clinics like ours. It put the onus on me to do something.

I learned from Gandhi that I cannot depend on government, I cannot depend on the policy, I have to act myself.

I said, I would not worry about making money, I would rather lose funding on this. So, we started. I read 400+ papers; I spent over 1,000 hours reading about disparities. And I realized that it’s not complicated. There are five pillars to eliminate disparity: access to care for financial reasons, access to biomarker testing or precision medicine, access to social determinants of health, access to cancer screening, and trials. If we focus on these five, we can at least bring that number from 34% to 20%, if not lower.

So, we put that plan in place. I dedicated three employees whose only role is to ensure that not a single patient has to take financial burden from my practice. And we showed it’s doable.

This has now become my mission for the last quarter of my life.
 

In 2020, Dr. Patel published a book on dying well titled “Between Life and Death.” It’s framed as a series of his conversations with a former patient, Harry Falls. Harry wanted to understand death better, so Dr. Patel narrated five patient stories, drawing the threads together to help Harry face the inevitable. Dr. Patel now uses a similar approach to train clinicians on having meaningful end-of-life conversations with patients.

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Q: Why did you feel the need to write a book about dying?

A: The more I’ve witnessed, the more I’m convinced that there are things that we don’t know about this process, which needs to be explored much more. However, I do feel that there’s a power within all of us to steer the process of leaving this world.

Before I sat down with Harry, I loved to counsel patients, but I didn’t have any structural ideas. It was Harry himself who told me that I now had a simple way to explain dying to a much larger audience.
 

Q: What is your secret for fitting everything into your life?

A: I’ll tell you, it’s very simple. If I put my soul, heart, mind, actions, and language on the one plane and don’t let my brain and conditioning influence my choices, then I live in the moment. Whenever I let my conditioned mind take all the decisions, those are crooked, because you know, we’re selfish creatures – we can use what we call the convenient lie to hide inconvenient truth. And I try not to do that. I mean, it’s been a journey. It didn’t come overnight. I learned. And I feel that over all these years, the only thing that rewarded me, that opened the door of where I am today, was pure, selfless process, whether it’s the act of talking, speaking, or doing.

Physicians treating Hodgkin lymphoma should not delay potentially curative allogeneic hematopoietic cell transplantation (allo-HCT) over fears of checkpoint inhibitor (CPI)–related graft-versus-host disease (GVHD), said a speaker at the annual meeting European Society for Blood and Bone Marrow Transplantation.

In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York. 

“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”

Perales_MiguelAngel_NY_web.jpg

To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.

Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).

“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)

At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor. 

They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).

However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”

The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.

Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”

Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.

The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.

“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.” 

However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.” 

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

Physicians treating Hodgkin lymphoma should not delay potentially curative allogeneic hematopoietic cell transplantation (allo-HCT) over fears of checkpoint inhibitor (CPI)–related graft-versus-host disease (GVHD), said a speaker at the annual meeting European Society for Blood and Bone Marrow Transplantation.

In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York. 

“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”

Perales_MiguelAngel_NY_web.jpg

To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.

Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).

“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)

At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor. 

They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).

However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”

The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.

Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”

Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.

The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.

“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.” 

However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.” 

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

Physicians treating Hodgkin lymphoma should not delay potentially curative allogeneic hematopoietic cell transplantation (allo-HCT) over fears of checkpoint inhibitor (CPI)–related graft-versus-host disease (GVHD), said a speaker at the annual meeting European Society for Blood and Bone Marrow Transplantation.

In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York. 

“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”

Perales_MiguelAngel_NY_web.jpg

To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.

Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).

“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)

At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor. 

They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).

However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”

The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.

Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”

Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.

The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.

“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.” 

However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.” 

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.