User login
DLBCL: Major new treatment breakthroughs
Significant breakthroughs have come in just the past few weeks and months, through the use of CAR T-cell and immunotherapies and with the approval in April by the Food and Drug Administration of polatuzumab for frontline DLBCL.
“Until the publishing of data from the POLARIX study (NCT03274492), which led to the approval of polatuzumab vedotin plus rituximab-cyclophosphamide, doxorubicin, and prednisone (pola + R-CHP), we had not had a breakthrough in frontline DLBCL therapies since the addition of rituximab 22 years ago,” said Dr. Charalambos Andreadis, MD, of the University of California at San Francisco’s Helen Diller Family Comprehensive Cancer Center.
“Pola + R-CHP is an improvement over the standard-of-care treatment, R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone), giving treatment naive patients an increase in PFS without an increase in side effects,” Dr. Andreadis said.
R-CHP-polatuzumab was approved only for patients with an International Prognostic Indices score between 2 and 5, leaving patients with IPI scores of 0 or 1 with the frontline standard of care (SoC) treatment of R-CHOP, which has a cure rate of between 60% and 70%.
“The highest likelihood of relapse is in the first year following treatment. After 2 years in remission, patients’ chance of relapsing is the same as the general populations’ chance of getting DLBCL for the first time. This is why even a slight increase in the progression-free survival rate with the addition of pola is so significant,” Dr. Andreadis noted.
Historically, patients with relapsed or refractory (RR) DLBCL who did not respond to R-CHOP or who experienced disease relapse less than a year after primary intervention were treated with alternative chemotherapy regimens, often followed by autologous stem cell transplants (ASCT). Randomized control studies have shown that CAR T-cell therapies yield higher success rates than chemotherapy and ASCT, leading to the SoC in RR patients being CAR-T cell therapy directly following failed primary treatment.
“There are many new CAR T-cell platforms in development, as well as novel combination strategies that aim to target critical genetic pathways,” Kieron Dunleavy, MD, professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital, said in an interview. “While access to CAR T-cell therapies is becoming easier and more feasible in many centers, fast access continues to be an issue for many patients, often depending on geography and socioeconomic factors.”
Asked about the latest breakthroughs in treating DLBCL, Dr. Dunleavy said, “A significant proportion of patients with relapsed or refractory DLBCL do not have easy access to CAR T-cell therapies, so this needs to be addressed and improved. Sometimes the rapidity of clinical progression in DLBCL can make these therapies challenging to deliver, considering logistical issues like apheresis and insurance approvals, which are frequently complex. This highlights the need for alternative and ‘easier to deliver’ CAR-T cells and our continued prioritization of developing alternative effective agents for DLBCL.
“Currently, commercially approved CAR T-cells in DLBCL target the CD-19 marker on lymphoma cells but CAR T-cells targeting other and more than one antigen as well as alternative anti CD19 agents like loncastuximab and tafasitamab are similarly FDA approved and available for patients,” Dr. Dunleavy concluded.
Dr. Dunleavy is affiliated with the MedStar Georgetown Lymphoma group, where Rep. Raskin publicly announced that he had completed 4 months of chemotherapy treatment for DLBCL. On April 27, in an open letter to the U.S. public, he wrote that he rang the bell at MedStar to mark his preliminary diagnosis of being “in remission,” with a “90% prognosis of no relapse.”
Interviewed about the latest advances in treating DLBCL, Jason Westin, MD, associate professor of lymphoma and myeloma at the MD Anderson Cancer Center in Houston, said that even with improvements in overall survival possible with CAR T-cell therapies, “usually, a clinical trial should be considered strongly, as it is often the best option for patients, both in a newly diagnosed or in a relapsed setting, as they allow access to tomorrow’s breakthrough therapies today.”
Dr. Westin cited the example of bispecific T-cell engagers (BITE) as a promising therapy that is available to patients in clinical trials. These agents bind to one side to the lymphoma cell, but they also have a binding arm for T-cells, so they activate a patient’s own immune cells to kill lymphoma cells, in some cases offering a cure when CAR T-cell therapy has failed.
The first BITE to be approved, mosunetuzumab, is authorized only for the treatment of follicular lymphoma. However, data from a recent clinical study indicated that the agent yields complete responses in 24% of heavily pretreated patients with RR DLBCL.
Another BITE, glofitamab, was approved in Canada in March 2023 for use in RR DLBCL. Based on its high efficacy, it soon may be approved elsewhere.
Dr. Andreadis noted, “We are finally at a point where for both treatment naive and RR DLBCL patients, there are several promising options on the horizon that don’t involve ASCT. Furthermore, these breakthroughs reinforce each other, as there are studies in which therapies like BITE are being brought to the front line and pola to RR cases.”
The growing field of new frontline and RR DLBCL therapies lend credence to the optimism of specialists who treat DLBCL – and to the sanguine note that Congressman Raskin struck in published comments about his treatment for DLBCL.
Dr. Andreadis reported ties with BMS, Novartis, Roche, Genmab, Merck, Gilead, AbbVie, and J&J. Dr. Dunleavy disclosed relationships with ONO Pharmaceuticals, Kymera, Merck, Genentech, AstraZeneca, Amgen, ADC Therapeutics, MorphoSys and Incyte, Kite/Gilead, Cellectar. Dr. Westin reported ties with Kite/Gilead, BMS, Novartis, Genentech, AstraZeneca, Morphosys/Incyte, ADC Therapeutics, Kymera, Nurix, and MonteRosa.
Significant breakthroughs have come in just the past few weeks and months, through the use of CAR T-cell and immunotherapies and with the approval in April by the Food and Drug Administration of polatuzumab for frontline DLBCL.
“Until the publishing of data from the POLARIX study (NCT03274492), which led to the approval of polatuzumab vedotin plus rituximab-cyclophosphamide, doxorubicin, and prednisone (pola + R-CHP), we had not had a breakthrough in frontline DLBCL therapies since the addition of rituximab 22 years ago,” said Dr. Charalambos Andreadis, MD, of the University of California at San Francisco’s Helen Diller Family Comprehensive Cancer Center.
“Pola + R-CHP is an improvement over the standard-of-care treatment, R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone), giving treatment naive patients an increase in PFS without an increase in side effects,” Dr. Andreadis said.
R-CHP-polatuzumab was approved only for patients with an International Prognostic Indices score between 2 and 5, leaving patients with IPI scores of 0 or 1 with the frontline standard of care (SoC) treatment of R-CHOP, which has a cure rate of between 60% and 70%.
“The highest likelihood of relapse is in the first year following treatment. After 2 years in remission, patients’ chance of relapsing is the same as the general populations’ chance of getting DLBCL for the first time. This is why even a slight increase in the progression-free survival rate with the addition of pola is so significant,” Dr. Andreadis noted.
Historically, patients with relapsed or refractory (RR) DLBCL who did not respond to R-CHOP or who experienced disease relapse less than a year after primary intervention were treated with alternative chemotherapy regimens, often followed by autologous stem cell transplants (ASCT). Randomized control studies have shown that CAR T-cell therapies yield higher success rates than chemotherapy and ASCT, leading to the SoC in RR patients being CAR-T cell therapy directly following failed primary treatment.
“There are many new CAR T-cell platforms in development, as well as novel combination strategies that aim to target critical genetic pathways,” Kieron Dunleavy, MD, professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital, said in an interview. “While access to CAR T-cell therapies is becoming easier and more feasible in many centers, fast access continues to be an issue for many patients, often depending on geography and socioeconomic factors.”
Asked about the latest breakthroughs in treating DLBCL, Dr. Dunleavy said, “A significant proportion of patients with relapsed or refractory DLBCL do not have easy access to CAR T-cell therapies, so this needs to be addressed and improved. Sometimes the rapidity of clinical progression in DLBCL can make these therapies challenging to deliver, considering logistical issues like apheresis and insurance approvals, which are frequently complex. This highlights the need for alternative and ‘easier to deliver’ CAR-T cells and our continued prioritization of developing alternative effective agents for DLBCL.
“Currently, commercially approved CAR T-cells in DLBCL target the CD-19 marker on lymphoma cells but CAR T-cells targeting other and more than one antigen as well as alternative anti CD19 agents like loncastuximab and tafasitamab are similarly FDA approved and available for patients,” Dr. Dunleavy concluded.
Dr. Dunleavy is affiliated with the MedStar Georgetown Lymphoma group, where Rep. Raskin publicly announced that he had completed 4 months of chemotherapy treatment for DLBCL. On April 27, in an open letter to the U.S. public, he wrote that he rang the bell at MedStar to mark his preliminary diagnosis of being “in remission,” with a “90% prognosis of no relapse.”
Interviewed about the latest advances in treating DLBCL, Jason Westin, MD, associate professor of lymphoma and myeloma at the MD Anderson Cancer Center in Houston, said that even with improvements in overall survival possible with CAR T-cell therapies, “usually, a clinical trial should be considered strongly, as it is often the best option for patients, both in a newly diagnosed or in a relapsed setting, as they allow access to tomorrow’s breakthrough therapies today.”
Dr. Westin cited the example of bispecific T-cell engagers (BITE) as a promising therapy that is available to patients in clinical trials. These agents bind to one side to the lymphoma cell, but they also have a binding arm for T-cells, so they activate a patient’s own immune cells to kill lymphoma cells, in some cases offering a cure when CAR T-cell therapy has failed.
The first BITE to be approved, mosunetuzumab, is authorized only for the treatment of follicular lymphoma. However, data from a recent clinical study indicated that the agent yields complete responses in 24% of heavily pretreated patients with RR DLBCL.
Another BITE, glofitamab, was approved in Canada in March 2023 for use in RR DLBCL. Based on its high efficacy, it soon may be approved elsewhere.
Dr. Andreadis noted, “We are finally at a point where for both treatment naive and RR DLBCL patients, there are several promising options on the horizon that don’t involve ASCT. Furthermore, these breakthroughs reinforce each other, as there are studies in which therapies like BITE are being brought to the front line and pola to RR cases.”
The growing field of new frontline and RR DLBCL therapies lend credence to the optimism of specialists who treat DLBCL – and to the sanguine note that Congressman Raskin struck in published comments about his treatment for DLBCL.
Dr. Andreadis reported ties with BMS, Novartis, Roche, Genmab, Merck, Gilead, AbbVie, and J&J. Dr. Dunleavy disclosed relationships with ONO Pharmaceuticals, Kymera, Merck, Genentech, AstraZeneca, Amgen, ADC Therapeutics, MorphoSys and Incyte, Kite/Gilead, Cellectar. Dr. Westin reported ties with Kite/Gilead, BMS, Novartis, Genentech, AstraZeneca, Morphosys/Incyte, ADC Therapeutics, Kymera, Nurix, and MonteRosa.
Significant breakthroughs have come in just the past few weeks and months, through the use of CAR T-cell and immunotherapies and with the approval in April by the Food and Drug Administration of polatuzumab for frontline DLBCL.
“Until the publishing of data from the POLARIX study (NCT03274492), which led to the approval of polatuzumab vedotin plus rituximab-cyclophosphamide, doxorubicin, and prednisone (pola + R-CHP), we had not had a breakthrough in frontline DLBCL therapies since the addition of rituximab 22 years ago,” said Dr. Charalambos Andreadis, MD, of the University of California at San Francisco’s Helen Diller Family Comprehensive Cancer Center.
“Pola + R-CHP is an improvement over the standard-of-care treatment, R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone), giving treatment naive patients an increase in PFS without an increase in side effects,” Dr. Andreadis said.
R-CHP-polatuzumab was approved only for patients with an International Prognostic Indices score between 2 and 5, leaving patients with IPI scores of 0 or 1 with the frontline standard of care (SoC) treatment of R-CHOP, which has a cure rate of between 60% and 70%.
“The highest likelihood of relapse is in the first year following treatment. After 2 years in remission, patients’ chance of relapsing is the same as the general populations’ chance of getting DLBCL for the first time. This is why even a slight increase in the progression-free survival rate with the addition of pola is so significant,” Dr. Andreadis noted.
Historically, patients with relapsed or refractory (RR) DLBCL who did not respond to R-CHOP or who experienced disease relapse less than a year after primary intervention were treated with alternative chemotherapy regimens, often followed by autologous stem cell transplants (ASCT). Randomized control studies have shown that CAR T-cell therapies yield higher success rates than chemotherapy and ASCT, leading to the SoC in RR patients being CAR-T cell therapy directly following failed primary treatment.
“There are many new CAR T-cell platforms in development, as well as novel combination strategies that aim to target critical genetic pathways,” Kieron Dunleavy, MD, professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital, said in an interview. “While access to CAR T-cell therapies is becoming easier and more feasible in many centers, fast access continues to be an issue for many patients, often depending on geography and socioeconomic factors.”
Asked about the latest breakthroughs in treating DLBCL, Dr. Dunleavy said, “A significant proportion of patients with relapsed or refractory DLBCL do not have easy access to CAR T-cell therapies, so this needs to be addressed and improved. Sometimes the rapidity of clinical progression in DLBCL can make these therapies challenging to deliver, considering logistical issues like apheresis and insurance approvals, which are frequently complex. This highlights the need for alternative and ‘easier to deliver’ CAR-T cells and our continued prioritization of developing alternative effective agents for DLBCL.
“Currently, commercially approved CAR T-cells in DLBCL target the CD-19 marker on lymphoma cells but CAR T-cells targeting other and more than one antigen as well as alternative anti CD19 agents like loncastuximab and tafasitamab are similarly FDA approved and available for patients,” Dr. Dunleavy concluded.
Dr. Dunleavy is affiliated with the MedStar Georgetown Lymphoma group, where Rep. Raskin publicly announced that he had completed 4 months of chemotherapy treatment for DLBCL. On April 27, in an open letter to the U.S. public, he wrote that he rang the bell at MedStar to mark his preliminary diagnosis of being “in remission,” with a “90% prognosis of no relapse.”
Interviewed about the latest advances in treating DLBCL, Jason Westin, MD, associate professor of lymphoma and myeloma at the MD Anderson Cancer Center in Houston, said that even with improvements in overall survival possible with CAR T-cell therapies, “usually, a clinical trial should be considered strongly, as it is often the best option for patients, both in a newly diagnosed or in a relapsed setting, as they allow access to tomorrow’s breakthrough therapies today.”
Dr. Westin cited the example of bispecific T-cell engagers (BITE) as a promising therapy that is available to patients in clinical trials. These agents bind to one side to the lymphoma cell, but they also have a binding arm for T-cells, so they activate a patient’s own immune cells to kill lymphoma cells, in some cases offering a cure when CAR T-cell therapy has failed.
The first BITE to be approved, mosunetuzumab, is authorized only for the treatment of follicular lymphoma. However, data from a recent clinical study indicated that the agent yields complete responses in 24% of heavily pretreated patients with RR DLBCL.
Another BITE, glofitamab, was approved in Canada in March 2023 for use in RR DLBCL. Based on its high efficacy, it soon may be approved elsewhere.
Dr. Andreadis noted, “We are finally at a point where for both treatment naive and RR DLBCL patients, there are several promising options on the horizon that don’t involve ASCT. Furthermore, these breakthroughs reinforce each other, as there are studies in which therapies like BITE are being brought to the front line and pola to RR cases.”
The growing field of new frontline and RR DLBCL therapies lend credence to the optimism of specialists who treat DLBCL – and to the sanguine note that Congressman Raskin struck in published comments about his treatment for DLBCL.
Dr. Andreadis reported ties with BMS, Novartis, Roche, Genmab, Merck, Gilead, AbbVie, and J&J. Dr. Dunleavy disclosed relationships with ONO Pharmaceuticals, Kymera, Merck, Genentech, AstraZeneca, Amgen, ADC Therapeutics, MorphoSys and Incyte, Kite/Gilead, Cellectar. Dr. Westin reported ties with Kite/Gilead, BMS, Novartis, Genentech, AstraZeneca, Morphosys/Incyte, ADC Therapeutics, Kymera, Nurix, and MonteRosa.
Experts debate reducing ASCT for multiple myeloma
NEW YORK –
Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.
A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy.
Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.
“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.
In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.
“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.
He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.
“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.
Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.
“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.
Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.
NEW YORK –
Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.
A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy.
Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.
“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.
In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.
“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.
He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.
“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.
Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.
“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.
Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.
NEW YORK –
Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.
A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy.
Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.
“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.
In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.
“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.
He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.
“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.
Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.
“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.
Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.
AT 2023 GREAT DEBATES AND UPDATES HEMATOLOGIC MALIGNANCIES CONFERENCE
Frontline CLL treatment: Avoiding adverse events
NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.
Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.
said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”
Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.
The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.
Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.
“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”
The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”
Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.
NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.
Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.
said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”
Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.
The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.
Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.
“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”
The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”
Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.
NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.
Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.
said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”
Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.
The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.
Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.
“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”
The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”
Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.
AT 2023 GREAT DEBATES AND UPDATES HEMATOLOGIC MALIGNANCIES CONFERENCE
Relapsed CLL: New approaches prolong survival
NEW YORK –
“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.
The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.
Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”
Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.
The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).
Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.
“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.
Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”
Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”
Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
NEW YORK –
“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.
The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.
Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”
Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.
The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).
Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.
“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.
Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”
Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”
Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
NEW YORK –
“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.
The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.
Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”
Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.
The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).
Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.
“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.
Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”
Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”
Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
AT 2023 GREAT DEBATES AND UPDATES HEMATOLOGIC MALIGNANCIES CONFERENCE
MRD: Powerful metric for CLL research
“MRD measurement is now a key feature of CLL clinical trials reporting. It can change CLL care by enabling approval of medication use in the wider (nontrial) patient population based on MRD data, without having to wait (ever-increasing) times for conventional trial outcomes, such as progression-free survival [PFS],” said study author Tahla Munir MD, of the department of hematology, at the Leeds (England) Teaching Hospitals of the National Health Service Trust.
“It also has potential to direct our treatment duration and follow-up strategies based on MRD results taken during or at the end of treatment, and to direct new treatment strategies, such as intermittent (as opposed to fixed-duration or continuous) treatment,” Dr. Munir said in an interview.
The review study defined MRD according to the detectable proportion of residual CLL cells. (Current international consensus for undetectable is U-MRD4 1 leukemic cell in 10,000 leukocytes.) The advantages and disadvantages of different MRD assays were analyzed. Multiparameter flow cytometry, an older technology, proved less sensitive to newer tests. It is reliable measuring to a sensitivity of U-MRD4 and more widely available than next-generation real-time quantitative polymerase chain reaction tests (NG-PCR).
“NG-PCR has the most potential for use in laboratory practice. It doesn’t require patient-specific primers and can detect around 1 CLL cell in 1x106 leukocytes. The biggest challenge is laboratory sequencing and bioinformatic capacity,” said lead study author Amelia Fisher, clinical research fellow at the division of cancer studies and pathology, University of Leeds.
“Multiple wells are required to gather adequate data to match the sensitivity of NGS. As this technology improves to match NGS sensitivity using fewer wells, once primers (bespoke to each patient) are designed it will provide a simple to use, rapid and easily reportable MRD tool, that could be scaled up in the event of MRD testing becoming routine practice,” explained Dr. Fisher.
The study also demonstrated how MRD can offer more in-depth insights into the success of treatments versus PFS. In the MURANO clinical trial, which compared venetoclax-rituximab treatment with standard chemoimmunotherapy (SC) to treat relapsed or refractory CLL, the PFS and overall survival (OS) remained significantly prolonged in the VR group at 5 years after therapy.
Analysis of MRD levels in the VR arm demonstrated that those with U-MRD4 had superior OS, with survival at 5 years of 95.3%, compared with those with higher rates of MRD (72.9%). A slower rate of MRD doubling time in the VR-treated patients, compared with the SC-treated patients, also buttressed the notion of moving from SC to VR treatment for the general CLL patient population.
Researchers cautioned that “a lot of the data is very recent, and therefore we do not have conventional trial outcomes, e.g., PFS and OS for all the studies. Some of the data we have is over a relatively short time period.”
An independent expert not associated with the study, Alessandra Ferrajoli, MD, associate medical director of the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston, expressed agreement with the study’s main findings.
“It is very likely that MRD assessment will be incorporated as a standard measurement of treatment efficacy in patients with CLL in the near future. The technologies have evolved to high levels of sensitivity, and the methods are being successfully harmonized and standardized,” she said.
Neither the study authors nor Dr. Ferrajoli reported conflicts of interest.
“MRD measurement is now a key feature of CLL clinical trials reporting. It can change CLL care by enabling approval of medication use in the wider (nontrial) patient population based on MRD data, without having to wait (ever-increasing) times for conventional trial outcomes, such as progression-free survival [PFS],” said study author Tahla Munir MD, of the department of hematology, at the Leeds (England) Teaching Hospitals of the National Health Service Trust.
“It also has potential to direct our treatment duration and follow-up strategies based on MRD results taken during or at the end of treatment, and to direct new treatment strategies, such as intermittent (as opposed to fixed-duration or continuous) treatment,” Dr. Munir said in an interview.
The review study defined MRD according to the detectable proportion of residual CLL cells. (Current international consensus for undetectable is U-MRD4 1 leukemic cell in 10,000 leukocytes.) The advantages and disadvantages of different MRD assays were analyzed. Multiparameter flow cytometry, an older technology, proved less sensitive to newer tests. It is reliable measuring to a sensitivity of U-MRD4 and more widely available than next-generation real-time quantitative polymerase chain reaction tests (NG-PCR).
“NG-PCR has the most potential for use in laboratory practice. It doesn’t require patient-specific primers and can detect around 1 CLL cell in 1x106 leukocytes. The biggest challenge is laboratory sequencing and bioinformatic capacity,” said lead study author Amelia Fisher, clinical research fellow at the division of cancer studies and pathology, University of Leeds.
“Multiple wells are required to gather adequate data to match the sensitivity of NGS. As this technology improves to match NGS sensitivity using fewer wells, once primers (bespoke to each patient) are designed it will provide a simple to use, rapid and easily reportable MRD tool, that could be scaled up in the event of MRD testing becoming routine practice,” explained Dr. Fisher.
The study also demonstrated how MRD can offer more in-depth insights into the success of treatments versus PFS. In the MURANO clinical trial, which compared venetoclax-rituximab treatment with standard chemoimmunotherapy (SC) to treat relapsed or refractory CLL, the PFS and overall survival (OS) remained significantly prolonged in the VR group at 5 years after therapy.
Analysis of MRD levels in the VR arm demonstrated that those with U-MRD4 had superior OS, with survival at 5 years of 95.3%, compared with those with higher rates of MRD (72.9%). A slower rate of MRD doubling time in the VR-treated patients, compared with the SC-treated patients, also buttressed the notion of moving from SC to VR treatment for the general CLL patient population.
Researchers cautioned that “a lot of the data is very recent, and therefore we do not have conventional trial outcomes, e.g., PFS and OS for all the studies. Some of the data we have is over a relatively short time period.”
An independent expert not associated with the study, Alessandra Ferrajoli, MD, associate medical director of the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston, expressed agreement with the study’s main findings.
“It is very likely that MRD assessment will be incorporated as a standard measurement of treatment efficacy in patients with CLL in the near future. The technologies have evolved to high levels of sensitivity, and the methods are being successfully harmonized and standardized,” she said.
Neither the study authors nor Dr. Ferrajoli reported conflicts of interest.
“MRD measurement is now a key feature of CLL clinical trials reporting. It can change CLL care by enabling approval of medication use in the wider (nontrial) patient population based on MRD data, without having to wait (ever-increasing) times for conventional trial outcomes, such as progression-free survival [PFS],” said study author Tahla Munir MD, of the department of hematology, at the Leeds (England) Teaching Hospitals of the National Health Service Trust.
“It also has potential to direct our treatment duration and follow-up strategies based on MRD results taken during or at the end of treatment, and to direct new treatment strategies, such as intermittent (as opposed to fixed-duration or continuous) treatment,” Dr. Munir said in an interview.
The review study defined MRD according to the detectable proportion of residual CLL cells. (Current international consensus for undetectable is U-MRD4 1 leukemic cell in 10,000 leukocytes.) The advantages and disadvantages of different MRD assays were analyzed. Multiparameter flow cytometry, an older technology, proved less sensitive to newer tests. It is reliable measuring to a sensitivity of U-MRD4 and more widely available than next-generation real-time quantitative polymerase chain reaction tests (NG-PCR).
“NG-PCR has the most potential for use in laboratory practice. It doesn’t require patient-specific primers and can detect around 1 CLL cell in 1x106 leukocytes. The biggest challenge is laboratory sequencing and bioinformatic capacity,” said lead study author Amelia Fisher, clinical research fellow at the division of cancer studies and pathology, University of Leeds.
“Multiple wells are required to gather adequate data to match the sensitivity of NGS. As this technology improves to match NGS sensitivity using fewer wells, once primers (bespoke to each patient) are designed it will provide a simple to use, rapid and easily reportable MRD tool, that could be scaled up in the event of MRD testing becoming routine practice,” explained Dr. Fisher.
The study also demonstrated how MRD can offer more in-depth insights into the success of treatments versus PFS. In the MURANO clinical trial, which compared venetoclax-rituximab treatment with standard chemoimmunotherapy (SC) to treat relapsed or refractory CLL, the PFS and overall survival (OS) remained significantly prolonged in the VR group at 5 years after therapy.
Analysis of MRD levels in the VR arm demonstrated that those with U-MRD4 had superior OS, with survival at 5 years of 95.3%, compared with those with higher rates of MRD (72.9%). A slower rate of MRD doubling time in the VR-treated patients, compared with the SC-treated patients, also buttressed the notion of moving from SC to VR treatment for the general CLL patient population.
Researchers cautioned that “a lot of the data is very recent, and therefore we do not have conventional trial outcomes, e.g., PFS and OS for all the studies. Some of the data we have is over a relatively short time period.”
An independent expert not associated with the study, Alessandra Ferrajoli, MD, associate medical director of the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston, expressed agreement with the study’s main findings.
“It is very likely that MRD assessment will be incorporated as a standard measurement of treatment efficacy in patients with CLL in the near future. The technologies have evolved to high levels of sensitivity, and the methods are being successfully harmonized and standardized,” she said.
Neither the study authors nor Dr. Ferrajoli reported conflicts of interest.
FROM FRONTIERS IN ONCOLOGY
SCD meds: Why such ‘slow uptake’?
“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.
The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).
Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.
In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”
As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.
Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).
“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.
Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.
Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”
Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.
The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).
Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.
In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”
As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.
Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).
“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.
Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.
Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”
Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.
The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).
Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.
In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”
As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.
Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).
“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.
Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.
Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”
Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
Black women have higher state-level rates of TNBC
New national data on the occurrence of triple-negative breast cancer (TNBC) among different racial groups confirms that the disease is more common among Black women nationwide. A state-by-state analysis in the study, published online in JAMA Oncology, shows that these trends persist at the state level.
The analysis revealed that incidence rate ratios of TNBC were significantly higher among Black women, compared with White women, in all states with data on this population. Rates ranged from a low of 1.38 in Colorado to a high of 2.32 in Delaware.
The state-level disparities highlight gaps in physicians’ understanding of how social factors contribute to disparities in TNBC risk and the need “to develop effective preventative measures,” the study authors explain.
“We’ve realized for a long time that Black women have a higher incidence of TNBC. This is related to the genetic signature of the cancer. So that is not at all surprising,” said Arnold M. Baskies, MD, past chairman of the national board of directors of the American Cancer Society, Atlanta, who was not involved in the research. However, “the variance of TNBC among women from state to state is somewhat surprising.”
Existing research shows that TNBC is diagnosed more frequently among non-Hispanic Black women than among other populations in the United States, but it’s unclear whether these racial and ethnic disparities differ at the state level.
The authors identified 133,579 women with TNBC from the U.S. Cancer Statistics Public Use Research Database whose conditions were diagnosed from January 2015 through the end of December 2019. Most patients (64.5%) were White, 21.5% were Black, nearly 10% were Hispanic, 3.7% were Asian or Pacific Islander, and 0.6% were American Indian or Alaska Native. States with fewer than 30 cases were excluded, as was Nevada, owing to concerns regarding data quality. That left eight states for American Indian or Alaska Natives, 22 for Asian or Pacific Islanders, 35 for Hispanic women, 38 for Black women, and 50 for White women.
Overall, the incidence ratios of TNBC were highest among Black women (IR, 25.2 per 100,000), followed by White women (IR, 12.9 per 100,000), American Indian or Alaska Native women (IR, 11.2 per 100,000), Hispanic women (IR, 11.1 per 100,000 women), and Asian or Pacific Islander (IR, 9.0 per 100,000) women.
The authors also uncovered significant state-by-state variations in TNBC incidence by racial and ethnic groups. The lowest IR rates occurred among Asian or Pacific Islander women in Oregon and Pennsylvania – fewer than 7 per 100,000 women – and the highest occurred among Black women in Delaware, Missouri, Louisiana, and Mississippi – more than 29 per 100,000 women.
In the 38 states for which data on Black women were available, IR rates were significantly higher among Black women in all 38, compared with White women. The IR rates ranged from a low of 1.38 (IR, 17.4 per 100 000 women) in Colorado to a high of 2.32 (IR, 32.0 per 100 000 women) in Delaware.
While genetics play a role in TNBC risk, “the substantial geographic variation we found within each racial and ethnic group is highly suggestive that there are structural, environmental, and social factors at play in determining women’s risk of TNBC,” said lead study author Hyuna Sung, PhD, senior principal scientist and cancer epidemiologist at the American Cancer Society, Atlanta.
Existing evidence indicates that Black and White women living in socioeconomically disadvantaged neighborhoods are at higher risk of developing more aggressive subtypes of breast cancer, Dr. Sung said. Another factor, Dr. Sung and co-authors note, is breastfeeding. Across races, women who breastfeed have lower rates of TNBC.
Getting more definitive answers as to what causes differences in TNBC rates across states and what strategies can help reduce these disparities will be difficult and requires more research. “We really need to do a better job at researching and treating TNBC to improve health care equality for all women,” Dr. Baskies said. “The mortality rates from this cancer are high, and we rely heavily on surgery and toxic chemotherapy to treat it.”
Dr. Sung agreed, noting that “the observed state variation in TNBC rates merits further studies with risk factor data at multiple levels to better understand the associations of social exposures with the risk of TNBC.”
In states such as Louisiana and Mississippi, which are known to have a disproportionately higher burden of many types of cancers, “addressing barriers to access to preventive care and empowering public health efforts to promote a healthy living environment are the best policy prescription that could be deduced from our results,” Dr. Sung concluded.
Dr. Baskies is on the board of directors of Anixa Biosciences, which is currently conducting a clinical trial of a TNBC vaccine at the Cleveland Clinic. Dr. Sung has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New national data on the occurrence of triple-negative breast cancer (TNBC) among different racial groups confirms that the disease is more common among Black women nationwide. A state-by-state analysis in the study, published online in JAMA Oncology, shows that these trends persist at the state level.
The analysis revealed that incidence rate ratios of TNBC were significantly higher among Black women, compared with White women, in all states with data on this population. Rates ranged from a low of 1.38 in Colorado to a high of 2.32 in Delaware.
The state-level disparities highlight gaps in physicians’ understanding of how social factors contribute to disparities in TNBC risk and the need “to develop effective preventative measures,” the study authors explain.
“We’ve realized for a long time that Black women have a higher incidence of TNBC. This is related to the genetic signature of the cancer. So that is not at all surprising,” said Arnold M. Baskies, MD, past chairman of the national board of directors of the American Cancer Society, Atlanta, who was not involved in the research. However, “the variance of TNBC among women from state to state is somewhat surprising.”
Existing research shows that TNBC is diagnosed more frequently among non-Hispanic Black women than among other populations in the United States, but it’s unclear whether these racial and ethnic disparities differ at the state level.
The authors identified 133,579 women with TNBC from the U.S. Cancer Statistics Public Use Research Database whose conditions were diagnosed from January 2015 through the end of December 2019. Most patients (64.5%) were White, 21.5% were Black, nearly 10% were Hispanic, 3.7% were Asian or Pacific Islander, and 0.6% were American Indian or Alaska Native. States with fewer than 30 cases were excluded, as was Nevada, owing to concerns regarding data quality. That left eight states for American Indian or Alaska Natives, 22 for Asian or Pacific Islanders, 35 for Hispanic women, 38 for Black women, and 50 for White women.
Overall, the incidence ratios of TNBC were highest among Black women (IR, 25.2 per 100,000), followed by White women (IR, 12.9 per 100,000), American Indian or Alaska Native women (IR, 11.2 per 100,000), Hispanic women (IR, 11.1 per 100,000 women), and Asian or Pacific Islander (IR, 9.0 per 100,000) women.
The authors also uncovered significant state-by-state variations in TNBC incidence by racial and ethnic groups. The lowest IR rates occurred among Asian or Pacific Islander women in Oregon and Pennsylvania – fewer than 7 per 100,000 women – and the highest occurred among Black women in Delaware, Missouri, Louisiana, and Mississippi – more than 29 per 100,000 women.
In the 38 states for which data on Black women were available, IR rates were significantly higher among Black women in all 38, compared with White women. The IR rates ranged from a low of 1.38 (IR, 17.4 per 100 000 women) in Colorado to a high of 2.32 (IR, 32.0 per 100 000 women) in Delaware.
While genetics play a role in TNBC risk, “the substantial geographic variation we found within each racial and ethnic group is highly suggestive that there are structural, environmental, and social factors at play in determining women’s risk of TNBC,” said lead study author Hyuna Sung, PhD, senior principal scientist and cancer epidemiologist at the American Cancer Society, Atlanta.
Existing evidence indicates that Black and White women living in socioeconomically disadvantaged neighborhoods are at higher risk of developing more aggressive subtypes of breast cancer, Dr. Sung said. Another factor, Dr. Sung and co-authors note, is breastfeeding. Across races, women who breastfeed have lower rates of TNBC.
Getting more definitive answers as to what causes differences in TNBC rates across states and what strategies can help reduce these disparities will be difficult and requires more research. “We really need to do a better job at researching and treating TNBC to improve health care equality for all women,” Dr. Baskies said. “The mortality rates from this cancer are high, and we rely heavily on surgery and toxic chemotherapy to treat it.”
Dr. Sung agreed, noting that “the observed state variation in TNBC rates merits further studies with risk factor data at multiple levels to better understand the associations of social exposures with the risk of TNBC.”
In states such as Louisiana and Mississippi, which are known to have a disproportionately higher burden of many types of cancers, “addressing barriers to access to preventive care and empowering public health efforts to promote a healthy living environment are the best policy prescription that could be deduced from our results,” Dr. Sung concluded.
Dr. Baskies is on the board of directors of Anixa Biosciences, which is currently conducting a clinical trial of a TNBC vaccine at the Cleveland Clinic. Dr. Sung has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New national data on the occurrence of triple-negative breast cancer (TNBC) among different racial groups confirms that the disease is more common among Black women nationwide. A state-by-state analysis in the study, published online in JAMA Oncology, shows that these trends persist at the state level.
The analysis revealed that incidence rate ratios of TNBC were significantly higher among Black women, compared with White women, in all states with data on this population. Rates ranged from a low of 1.38 in Colorado to a high of 2.32 in Delaware.
The state-level disparities highlight gaps in physicians’ understanding of how social factors contribute to disparities in TNBC risk and the need “to develop effective preventative measures,” the study authors explain.
“We’ve realized for a long time that Black women have a higher incidence of TNBC. This is related to the genetic signature of the cancer. So that is not at all surprising,” said Arnold M. Baskies, MD, past chairman of the national board of directors of the American Cancer Society, Atlanta, who was not involved in the research. However, “the variance of TNBC among women from state to state is somewhat surprising.”
Existing research shows that TNBC is diagnosed more frequently among non-Hispanic Black women than among other populations in the United States, but it’s unclear whether these racial and ethnic disparities differ at the state level.
The authors identified 133,579 women with TNBC from the U.S. Cancer Statistics Public Use Research Database whose conditions were diagnosed from January 2015 through the end of December 2019. Most patients (64.5%) were White, 21.5% were Black, nearly 10% were Hispanic, 3.7% were Asian or Pacific Islander, and 0.6% were American Indian or Alaska Native. States with fewer than 30 cases were excluded, as was Nevada, owing to concerns regarding data quality. That left eight states for American Indian or Alaska Natives, 22 for Asian or Pacific Islanders, 35 for Hispanic women, 38 for Black women, and 50 for White women.
Overall, the incidence ratios of TNBC were highest among Black women (IR, 25.2 per 100,000), followed by White women (IR, 12.9 per 100,000), American Indian or Alaska Native women (IR, 11.2 per 100,000), Hispanic women (IR, 11.1 per 100,000 women), and Asian or Pacific Islander (IR, 9.0 per 100,000) women.
The authors also uncovered significant state-by-state variations in TNBC incidence by racial and ethnic groups. The lowest IR rates occurred among Asian or Pacific Islander women in Oregon and Pennsylvania – fewer than 7 per 100,000 women – and the highest occurred among Black women in Delaware, Missouri, Louisiana, and Mississippi – more than 29 per 100,000 women.
In the 38 states for which data on Black women were available, IR rates were significantly higher among Black women in all 38, compared with White women. The IR rates ranged from a low of 1.38 (IR, 17.4 per 100 000 women) in Colorado to a high of 2.32 (IR, 32.0 per 100 000 women) in Delaware.
While genetics play a role in TNBC risk, “the substantial geographic variation we found within each racial and ethnic group is highly suggestive that there are structural, environmental, and social factors at play in determining women’s risk of TNBC,” said lead study author Hyuna Sung, PhD, senior principal scientist and cancer epidemiologist at the American Cancer Society, Atlanta.
Existing evidence indicates that Black and White women living in socioeconomically disadvantaged neighborhoods are at higher risk of developing more aggressive subtypes of breast cancer, Dr. Sung said. Another factor, Dr. Sung and co-authors note, is breastfeeding. Across races, women who breastfeed have lower rates of TNBC.
Getting more definitive answers as to what causes differences in TNBC rates across states and what strategies can help reduce these disparities will be difficult and requires more research. “We really need to do a better job at researching and treating TNBC to improve health care equality for all women,” Dr. Baskies said. “The mortality rates from this cancer are high, and we rely heavily on surgery and toxic chemotherapy to treat it.”
Dr. Sung agreed, noting that “the observed state variation in TNBC rates merits further studies with risk factor data at multiple levels to better understand the associations of social exposures with the risk of TNBC.”
In states such as Louisiana and Mississippi, which are known to have a disproportionately higher burden of many types of cancers, “addressing barriers to access to preventive care and empowering public health efforts to promote a healthy living environment are the best policy prescription that could be deduced from our results,” Dr. Sung concluded.
Dr. Baskies is on the board of directors of Anixa Biosciences, which is currently conducting a clinical trial of a TNBC vaccine at the Cleveland Clinic. Dr. Sung has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Zika virus still calls for preparedness and vaccine development
Warming U.S. temperatures, the resumption of travel, and new knowledge about Zika’s long-term effects on children signal that Zika prevention and vaccine development should be on public health officials’, doctors’, and communities’ radar, even when community infection is not occurring.
“Although we haven’t seen confirmed Zika virus circulation in the continental United States or its territories for several years, it’s still something that we are closely monitoring, particularly as we move into the summer months,” Erin Staples, MD, PhD, medical epidemiologist at the Arboviral Diseases Branch of the Centers for Disease Control and Prevention in Fort Collins, Colo., told this news organization.
“This is because cases are still being reported in other countries, particularly in South America. Travel to these places is increasing following the pandemic, leaving more potential for individuals who might have acquired the infection to come back and restart community transmission.”
How Zika might reemerge
The Aedes aegypti mosquito is the vector by which Zika spreads, and “during the COVID pandemic, these mosquitoes moved further north in the United States, into southern California, and were identified as far north as Washington, D.C.,” said Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at UCLA Medical Center in Los Angeles.
“On a population level, Americans have essentially no immunity to Zika from prior infection, and there is no vaccine yet approved. If individuals infected with Zika came into a U.S. region where the Aedes aegypti mosquito was present, that population could be very susceptible to infection spread and even another outbreak. This would be a confluence of bad circumstances, but that’s exactly what infectious disease specialists continue to be watchful about, especially because Zika is so dangerous for fetuses,” said Dr. Silverman.
How the public can prepare
The CDC recommends that pregnant women or women who plan to become pregnant avoid traveling to regions where there are currently outbreaks of Zika, but this is not the only way that individuals can protect themselves.
“The message we want to deliver to people is that in the United States, people are at risk for several mosquito-borne diseases every summer beyond just Zika,” Dr. Staples said. “It’s really important that people are instructed to make a habit of wearing EPA [U.S. Environmental Protection Agency)–registered insect repellents when they go outside. Right now, that is the single best tool that we have to prevent mosquito-borne diseases in the U.S.
“From a community standpoint, there are several emerging mosquito control methods that are being evaluated right now, such as genetic modification and irradiation of mosquitoes. These methods are aimed at producing sterile mosquitoes that are released into the wild to mate with the local mosquito population, which will render them infertile. This leads, over time, to suppression of the overall Aedes aegypti mosquito population – the main vector of Zika transmission,” said Dr. Staples.
Monica Gandhi, MD, MPH, professor of medicine and associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco, encourages her patients to wear mosquito repellent but cautioned that “there’s no antiviral that you can take for Zika. Until we have a vaccine, the key to controlling/preventing Zika is controlling the mosquitoes that spread the virus.”
Vaccines
The National Institute of Allergy and Infectious Diseases (NIAID) is currently investigating a variety of Zika vaccines, including a DNA-based vaccine, (phase 2), a purified inactivated virus vaccine (phase 1), live attenuated vaccines (phase 2), and mRNA vaccines (phase 2).
“I’m most excited about mRNA vaccines because they help patients produce a lot of proteins. The protein from a typical protein-adjuvant vaccine will break down, and patients can only raise an immune response to whatever proteins are left. On the other hand, mRNA vaccines provide the body [with] a recipe to make the protein from the pathogen in high amounts, so that a strong immune response can be raised for protection,” noted Dr. Gandhi.
Moderna’s mRNA-1893 vaccine was recently studied in a randomized, observer-blind, controlled, phase 1 trial among 120 adults in the United States and Puerto Rico, the results of which were published online in The Lancet. “The vaccine was found to be generally well tolerated with no serious adverse events considered related to vaccine. Furthermore, the vaccine was able to generate a potent immune response that was capable of neutralizing the virus in vitro,” said Brett Leav, MD, executive director of clinical development for public health vaccines at Moderna.
“Our mRNA platform technology ... can be very helpful against emerging pandemic threats, as we saw in response to COVID-19. What is unique in our approach is that if the genetic sequence of the virus is known, we can quickly generate vaccines to test for their capability to generate a functional immune response. In the case of the mRNA-1893 trial, the vaccine was developed with antigens that were present in the strain of virus circulating in 2016, but we could easily match whatever strain reemerges,” said Dr. Leav.
A phase 2 trial to confirm the dose of mRNA-1893 in a larger study population is underway.
Although it’s been demonstrated that Moderna’s mRNA vaccine is safe and effective, moving from a phase 2 to a phase 3 study presents a challenge, given the fact that currently, the disease burden from Zika is low. If an outbreak were to occur in the future, these mRNA vaccines could potentially be given emergency approval, as occurred during the COVID pandemic, according to Dr. Silverman.
If approved, provisionally or through a traditional route, the vaccine would “accelerate the ability to tamp down any further outbreaks, because vaccine-based immunity could be made available to a large portion of the population who were pregnant or planning a pregnancy, not just in the U.S. but also in these endemic areas,” said Dr. Silverman.
Takeaways from the last Zika outbreak
Practical steps such as mosquito eradication and development of vaccines are not the only takeaway from the recent Zika epidemics inside and outside the United States. A clearer picture of the short- and long-term stakes of the disease has emerged.
According to the CDC, most people who become infected with Zika experience only mild symptoms, such as fever, rash, headache, and muscle pain, but babies conceived by mothers infected with Zika are at risk for stillbirth, miscarriage, and microcephaly and other brain defects.
Although a pregnant woman who tests positive for Zika is in a very high-risk situation, “data show that only about 30% of mothers with Zika have a baby with birth defects. If a pregnant woman contracted Zika, what would happen is we would just do very close screening by ultrasound of the fetus. If microcephaly in utero or fetal brain defects were observed, then a mother would be counseled on her options,” said Dr. Gandhi.
Dr. Silverman noted that “new data on children who were exposed in utero and had normal exams, including head measurements when they were born, have raised concerns. In recently published long-term follow-up studies, even when children born to mothers infected with Zika during pregnancy had normal head growth at least 3 years after birth, they were still at risk for neurodevelopmental delay and behavioral disorders, including impact on coordination and executive function.
“This is another good reason to keep the potential risks of Zika active in the public’s consciousness and in public health planning.”
Dr. Silverman, Dr. Gandhi, and Dr. Staples have disclosed no relevant financial relationships. Dr. Leav is an employee of Moderna and owns stock in the company.
A version of this article originally appeared on Medscape.com.
Warming U.S. temperatures, the resumption of travel, and new knowledge about Zika’s long-term effects on children signal that Zika prevention and vaccine development should be on public health officials’, doctors’, and communities’ radar, even when community infection is not occurring.
“Although we haven’t seen confirmed Zika virus circulation in the continental United States or its territories for several years, it’s still something that we are closely monitoring, particularly as we move into the summer months,” Erin Staples, MD, PhD, medical epidemiologist at the Arboviral Diseases Branch of the Centers for Disease Control and Prevention in Fort Collins, Colo., told this news organization.
“This is because cases are still being reported in other countries, particularly in South America. Travel to these places is increasing following the pandemic, leaving more potential for individuals who might have acquired the infection to come back and restart community transmission.”
How Zika might reemerge
The Aedes aegypti mosquito is the vector by which Zika spreads, and “during the COVID pandemic, these mosquitoes moved further north in the United States, into southern California, and were identified as far north as Washington, D.C.,” said Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at UCLA Medical Center in Los Angeles.
“On a population level, Americans have essentially no immunity to Zika from prior infection, and there is no vaccine yet approved. If individuals infected with Zika came into a U.S. region where the Aedes aegypti mosquito was present, that population could be very susceptible to infection spread and even another outbreak. This would be a confluence of bad circumstances, but that’s exactly what infectious disease specialists continue to be watchful about, especially because Zika is so dangerous for fetuses,” said Dr. Silverman.
How the public can prepare
The CDC recommends that pregnant women or women who plan to become pregnant avoid traveling to regions where there are currently outbreaks of Zika, but this is not the only way that individuals can protect themselves.
“The message we want to deliver to people is that in the United States, people are at risk for several mosquito-borne diseases every summer beyond just Zika,” Dr. Staples said. “It’s really important that people are instructed to make a habit of wearing EPA [U.S. Environmental Protection Agency)–registered insect repellents when they go outside. Right now, that is the single best tool that we have to prevent mosquito-borne diseases in the U.S.
“From a community standpoint, there are several emerging mosquito control methods that are being evaluated right now, such as genetic modification and irradiation of mosquitoes. These methods are aimed at producing sterile mosquitoes that are released into the wild to mate with the local mosquito population, which will render them infertile. This leads, over time, to suppression of the overall Aedes aegypti mosquito population – the main vector of Zika transmission,” said Dr. Staples.
Monica Gandhi, MD, MPH, professor of medicine and associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco, encourages her patients to wear mosquito repellent but cautioned that “there’s no antiviral that you can take for Zika. Until we have a vaccine, the key to controlling/preventing Zika is controlling the mosquitoes that spread the virus.”
Vaccines
The National Institute of Allergy and Infectious Diseases (NIAID) is currently investigating a variety of Zika vaccines, including a DNA-based vaccine, (phase 2), a purified inactivated virus vaccine (phase 1), live attenuated vaccines (phase 2), and mRNA vaccines (phase 2).
“I’m most excited about mRNA vaccines because they help patients produce a lot of proteins. The protein from a typical protein-adjuvant vaccine will break down, and patients can only raise an immune response to whatever proteins are left. On the other hand, mRNA vaccines provide the body [with] a recipe to make the protein from the pathogen in high amounts, so that a strong immune response can be raised for protection,” noted Dr. Gandhi.
Moderna’s mRNA-1893 vaccine was recently studied in a randomized, observer-blind, controlled, phase 1 trial among 120 adults in the United States and Puerto Rico, the results of which were published online in The Lancet. “The vaccine was found to be generally well tolerated with no serious adverse events considered related to vaccine. Furthermore, the vaccine was able to generate a potent immune response that was capable of neutralizing the virus in vitro,” said Brett Leav, MD, executive director of clinical development for public health vaccines at Moderna.
“Our mRNA platform technology ... can be very helpful against emerging pandemic threats, as we saw in response to COVID-19. What is unique in our approach is that if the genetic sequence of the virus is known, we can quickly generate vaccines to test for their capability to generate a functional immune response. In the case of the mRNA-1893 trial, the vaccine was developed with antigens that were present in the strain of virus circulating in 2016, but we could easily match whatever strain reemerges,” said Dr. Leav.
A phase 2 trial to confirm the dose of mRNA-1893 in a larger study population is underway.
Although it’s been demonstrated that Moderna’s mRNA vaccine is safe and effective, moving from a phase 2 to a phase 3 study presents a challenge, given the fact that currently, the disease burden from Zika is low. If an outbreak were to occur in the future, these mRNA vaccines could potentially be given emergency approval, as occurred during the COVID pandemic, according to Dr. Silverman.
If approved, provisionally or through a traditional route, the vaccine would “accelerate the ability to tamp down any further outbreaks, because vaccine-based immunity could be made available to a large portion of the population who were pregnant or planning a pregnancy, not just in the U.S. but also in these endemic areas,” said Dr. Silverman.
Takeaways from the last Zika outbreak
Practical steps such as mosquito eradication and development of vaccines are not the only takeaway from the recent Zika epidemics inside and outside the United States. A clearer picture of the short- and long-term stakes of the disease has emerged.
According to the CDC, most people who become infected with Zika experience only mild symptoms, such as fever, rash, headache, and muscle pain, but babies conceived by mothers infected with Zika are at risk for stillbirth, miscarriage, and microcephaly and other brain defects.
Although a pregnant woman who tests positive for Zika is in a very high-risk situation, “data show that only about 30% of mothers with Zika have a baby with birth defects. If a pregnant woman contracted Zika, what would happen is we would just do very close screening by ultrasound of the fetus. If microcephaly in utero or fetal brain defects were observed, then a mother would be counseled on her options,” said Dr. Gandhi.
Dr. Silverman noted that “new data on children who were exposed in utero and had normal exams, including head measurements when they were born, have raised concerns. In recently published long-term follow-up studies, even when children born to mothers infected with Zika during pregnancy had normal head growth at least 3 years after birth, they were still at risk for neurodevelopmental delay and behavioral disorders, including impact on coordination and executive function.
“This is another good reason to keep the potential risks of Zika active in the public’s consciousness and in public health planning.”
Dr. Silverman, Dr. Gandhi, and Dr. Staples have disclosed no relevant financial relationships. Dr. Leav is an employee of Moderna and owns stock in the company.
A version of this article originally appeared on Medscape.com.
Warming U.S. temperatures, the resumption of travel, and new knowledge about Zika’s long-term effects on children signal that Zika prevention and vaccine development should be on public health officials’, doctors’, and communities’ radar, even when community infection is not occurring.
“Although we haven’t seen confirmed Zika virus circulation in the continental United States or its territories for several years, it’s still something that we are closely monitoring, particularly as we move into the summer months,” Erin Staples, MD, PhD, medical epidemiologist at the Arboviral Diseases Branch of the Centers for Disease Control and Prevention in Fort Collins, Colo., told this news organization.
“This is because cases are still being reported in other countries, particularly in South America. Travel to these places is increasing following the pandemic, leaving more potential for individuals who might have acquired the infection to come back and restart community transmission.”
How Zika might reemerge
The Aedes aegypti mosquito is the vector by which Zika spreads, and “during the COVID pandemic, these mosquitoes moved further north in the United States, into southern California, and were identified as far north as Washington, D.C.,” said Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at UCLA Medical Center in Los Angeles.
“On a population level, Americans have essentially no immunity to Zika from prior infection, and there is no vaccine yet approved. If individuals infected with Zika came into a U.S. region where the Aedes aegypti mosquito was present, that population could be very susceptible to infection spread and even another outbreak. This would be a confluence of bad circumstances, but that’s exactly what infectious disease specialists continue to be watchful about, especially because Zika is so dangerous for fetuses,” said Dr. Silverman.
How the public can prepare
The CDC recommends that pregnant women or women who plan to become pregnant avoid traveling to regions where there are currently outbreaks of Zika, but this is not the only way that individuals can protect themselves.
“The message we want to deliver to people is that in the United States, people are at risk for several mosquito-borne diseases every summer beyond just Zika,” Dr. Staples said. “It’s really important that people are instructed to make a habit of wearing EPA [U.S. Environmental Protection Agency)–registered insect repellents when they go outside. Right now, that is the single best tool that we have to prevent mosquito-borne diseases in the U.S.
“From a community standpoint, there are several emerging mosquito control methods that are being evaluated right now, such as genetic modification and irradiation of mosquitoes. These methods are aimed at producing sterile mosquitoes that are released into the wild to mate with the local mosquito population, which will render them infertile. This leads, over time, to suppression of the overall Aedes aegypti mosquito population – the main vector of Zika transmission,” said Dr. Staples.
Monica Gandhi, MD, MPH, professor of medicine and associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco, encourages her patients to wear mosquito repellent but cautioned that “there’s no antiviral that you can take for Zika. Until we have a vaccine, the key to controlling/preventing Zika is controlling the mosquitoes that spread the virus.”
Vaccines
The National Institute of Allergy and Infectious Diseases (NIAID) is currently investigating a variety of Zika vaccines, including a DNA-based vaccine, (phase 2), a purified inactivated virus vaccine (phase 1), live attenuated vaccines (phase 2), and mRNA vaccines (phase 2).
“I’m most excited about mRNA vaccines because they help patients produce a lot of proteins. The protein from a typical protein-adjuvant vaccine will break down, and patients can only raise an immune response to whatever proteins are left. On the other hand, mRNA vaccines provide the body [with] a recipe to make the protein from the pathogen in high amounts, so that a strong immune response can be raised for protection,” noted Dr. Gandhi.
Moderna’s mRNA-1893 vaccine was recently studied in a randomized, observer-blind, controlled, phase 1 trial among 120 adults in the United States and Puerto Rico, the results of which were published online in The Lancet. “The vaccine was found to be generally well tolerated with no serious adverse events considered related to vaccine. Furthermore, the vaccine was able to generate a potent immune response that was capable of neutralizing the virus in vitro,” said Brett Leav, MD, executive director of clinical development for public health vaccines at Moderna.
“Our mRNA platform technology ... can be very helpful against emerging pandemic threats, as we saw in response to COVID-19. What is unique in our approach is that if the genetic sequence of the virus is known, we can quickly generate vaccines to test for their capability to generate a functional immune response. In the case of the mRNA-1893 trial, the vaccine was developed with antigens that were present in the strain of virus circulating in 2016, but we could easily match whatever strain reemerges,” said Dr. Leav.
A phase 2 trial to confirm the dose of mRNA-1893 in a larger study population is underway.
Although it’s been demonstrated that Moderna’s mRNA vaccine is safe and effective, moving from a phase 2 to a phase 3 study presents a challenge, given the fact that currently, the disease burden from Zika is low. If an outbreak were to occur in the future, these mRNA vaccines could potentially be given emergency approval, as occurred during the COVID pandemic, according to Dr. Silverman.
If approved, provisionally or through a traditional route, the vaccine would “accelerate the ability to tamp down any further outbreaks, because vaccine-based immunity could be made available to a large portion of the population who were pregnant or planning a pregnancy, not just in the U.S. but also in these endemic areas,” said Dr. Silverman.
Takeaways from the last Zika outbreak
Practical steps such as mosquito eradication and development of vaccines are not the only takeaway from the recent Zika epidemics inside and outside the United States. A clearer picture of the short- and long-term stakes of the disease has emerged.
According to the CDC, most people who become infected with Zika experience only mild symptoms, such as fever, rash, headache, and muscle pain, but babies conceived by mothers infected with Zika are at risk for stillbirth, miscarriage, and microcephaly and other brain defects.
Although a pregnant woman who tests positive for Zika is in a very high-risk situation, “data show that only about 30% of mothers with Zika have a baby with birth defects. If a pregnant woman contracted Zika, what would happen is we would just do very close screening by ultrasound of the fetus. If microcephaly in utero or fetal brain defects were observed, then a mother would be counseled on her options,” said Dr. Gandhi.
Dr. Silverman noted that “new data on children who were exposed in utero and had normal exams, including head measurements when they were born, have raised concerns. In recently published long-term follow-up studies, even when children born to mothers infected with Zika during pregnancy had normal head growth at least 3 years after birth, they were still at risk for neurodevelopmental delay and behavioral disorders, including impact on coordination and executive function.
“This is another good reason to keep the potential risks of Zika active in the public’s consciousness and in public health planning.”
Dr. Silverman, Dr. Gandhi, and Dr. Staples have disclosed no relevant financial relationships. Dr. Leav is an employee of Moderna and owns stock in the company.
A version of this article originally appeared on Medscape.com.
Radiotherapy for early breast cancer: Sharp cutoff at age 70
say researchers reporting new data showing a sharp cut-off at age 70.
“In our study, one of the most significant variables in determining whether breast cancer patients who are close their 70th birthday are recommended standard-of-care radiation or de-escalated treatment is whether they show up a few months before or a few months after that 70th birthday,” commented study author Wesley J. Talcott, MD, of the department of therapeutic radiology at the Yale School of Medicine, New Haven, Conn.
The results show a trend in which radiation therapy is 50% less likely to be prescribed for patients age 70 and older with early-stage breast cancer, even when controlling for population size, patient demographics, and disease specific variables.
This suggests that oncologists are weighing the variable of age too heavily when deciding on adjuvant treatments, the authors suggest.
“In certain circumstances, breast cancer oncology providers are treating age like a binary categorical variable when selecting patients for treatments or diagnostic procedures, rather than the continuous variable that it is,” Dr. Talcott commented.
The study was published online in the International Journal of Radiation Oncology: Biology, Physics.
Approached for comment, Casey Chollet-Lipscomb, MD, radiation oncologist with Tennessee Oncology, Nashville, who was not associated with the study, agreed with its main finding.
“The study helps emphasize the importance of individualized care,” she said. “Increasing age is the most common risk factor for breast cancer, but breast cancer is an incredibly diverse disease. While you can observe trends based on age, every patient is unique, and they can’t be lumped into one bucket and prescribed treatment based on a strict age cutoff.”
The retrospective study included two cohorts of women identified in the National Cancer Data Base (2004-2017) all of whom underwent lumpectomy for early-stage breast cancer. All patients had “strong indications” for adjuvant treatment.
Patients in cohort 1 (n = 160,990) included women with estrogen-receptor negative cancer, tumor size greater than 3 cm, who were determined to be “appropriate” for radiation therapy.
Patients in cohort 2 (n = 394,946) had hormone-receptor positive cancer, tumor size greater than 5 mm, and were considered to be “appropriate” candidates for endocrine therapy.
Multivariable analysis was performed to control for comorbidity burden (measured by the Charlson-Deyo Comorbidity Index), race and ethnicity, insurance status, academic versus non-academic treatment center, median annual income of a patient’s area of residence, distance from the site of treatment, and pathology variables including number of lymph nodes sampled, histologic grade, and genomic risk score.
In cohort 1, radiation was recommended for 90%-92% of patients between the ages of 50-69; this dropped to 81% for those aged 70.
After MVA, it was determined that age difference was an independent predictor for adjuvant radiation recommendation only at age 70 versus 69 (odds ratio, 0.47; 95% confidence interval 0.39-0.57, P < .001).
For cohort 2, year-over-year age difference predicted endocrine therapy recommendation only at the juncture between age 70 versus 69 (OR, 0.86, 95% CI 0.74-0.99, P = .001).
“Our results don’t say that we should be increasing the amount of treatment for patients over the age [of] 70 or decreasing that patient treatment for patients younger than age 70. What we believe is that we need to be assessing physiologic age of our patients when treating patients,” Dr. Talcott said.
“We would do this by looking at not just how many years a patient has been on this Earth but also what their current health status is, how many good quality-of-life years they might have after treatment or without it, and what the patient wants in terms of burden of treatment. This is a much more valuable way to approach the allocation of treatments than using age alone,” he added.
Both Dr. Talcott and Dr. Chollet-Lipscomb agreed that a limitation of the study was a lack of data on how physicians decided on a specific treatment in each individual case, but they agree that even without this information the results were “significant.”
Dr. Chollet-Lipscomb also highlighted the factors other than age she would use to determine the best adjuvant treatment for a patient with early stage breast cancer, including the individual features of the tumor, how aggressive it looks under the microscope, what the receptor status is, and a patient’s overall performance status and comorbidities.
Dr. Talcott and Dr. Chollet-Lipscomb report no relevant financial relationships. The authors had no acknowledgement of research support for this study.
A version of this article first appeared on Medscape.com.
say researchers reporting new data showing a sharp cut-off at age 70.
“In our study, one of the most significant variables in determining whether breast cancer patients who are close their 70th birthday are recommended standard-of-care radiation or de-escalated treatment is whether they show up a few months before or a few months after that 70th birthday,” commented study author Wesley J. Talcott, MD, of the department of therapeutic radiology at the Yale School of Medicine, New Haven, Conn.
The results show a trend in which radiation therapy is 50% less likely to be prescribed for patients age 70 and older with early-stage breast cancer, even when controlling for population size, patient demographics, and disease specific variables.
This suggests that oncologists are weighing the variable of age too heavily when deciding on adjuvant treatments, the authors suggest.
“In certain circumstances, breast cancer oncology providers are treating age like a binary categorical variable when selecting patients for treatments or diagnostic procedures, rather than the continuous variable that it is,” Dr. Talcott commented.
The study was published online in the International Journal of Radiation Oncology: Biology, Physics.
Approached for comment, Casey Chollet-Lipscomb, MD, radiation oncologist with Tennessee Oncology, Nashville, who was not associated with the study, agreed with its main finding.
“The study helps emphasize the importance of individualized care,” she said. “Increasing age is the most common risk factor for breast cancer, but breast cancer is an incredibly diverse disease. While you can observe trends based on age, every patient is unique, and they can’t be lumped into one bucket and prescribed treatment based on a strict age cutoff.”
The retrospective study included two cohorts of women identified in the National Cancer Data Base (2004-2017) all of whom underwent lumpectomy for early-stage breast cancer. All patients had “strong indications” for adjuvant treatment.
Patients in cohort 1 (n = 160,990) included women with estrogen-receptor negative cancer, tumor size greater than 3 cm, who were determined to be “appropriate” for radiation therapy.
Patients in cohort 2 (n = 394,946) had hormone-receptor positive cancer, tumor size greater than 5 mm, and were considered to be “appropriate” candidates for endocrine therapy.
Multivariable analysis was performed to control for comorbidity burden (measured by the Charlson-Deyo Comorbidity Index), race and ethnicity, insurance status, academic versus non-academic treatment center, median annual income of a patient’s area of residence, distance from the site of treatment, and pathology variables including number of lymph nodes sampled, histologic grade, and genomic risk score.
In cohort 1, radiation was recommended for 90%-92% of patients between the ages of 50-69; this dropped to 81% for those aged 70.
After MVA, it was determined that age difference was an independent predictor for adjuvant radiation recommendation only at age 70 versus 69 (odds ratio, 0.47; 95% confidence interval 0.39-0.57, P < .001).
For cohort 2, year-over-year age difference predicted endocrine therapy recommendation only at the juncture between age 70 versus 69 (OR, 0.86, 95% CI 0.74-0.99, P = .001).
“Our results don’t say that we should be increasing the amount of treatment for patients over the age [of] 70 or decreasing that patient treatment for patients younger than age 70. What we believe is that we need to be assessing physiologic age of our patients when treating patients,” Dr. Talcott said.
“We would do this by looking at not just how many years a patient has been on this Earth but also what their current health status is, how many good quality-of-life years they might have after treatment or without it, and what the patient wants in terms of burden of treatment. This is a much more valuable way to approach the allocation of treatments than using age alone,” he added.
Both Dr. Talcott and Dr. Chollet-Lipscomb agreed that a limitation of the study was a lack of data on how physicians decided on a specific treatment in each individual case, but they agree that even without this information the results were “significant.”
Dr. Chollet-Lipscomb also highlighted the factors other than age she would use to determine the best adjuvant treatment for a patient with early stage breast cancer, including the individual features of the tumor, how aggressive it looks under the microscope, what the receptor status is, and a patient’s overall performance status and comorbidities.
Dr. Talcott and Dr. Chollet-Lipscomb report no relevant financial relationships. The authors had no acknowledgement of research support for this study.
A version of this article first appeared on Medscape.com.
say researchers reporting new data showing a sharp cut-off at age 70.
“In our study, one of the most significant variables in determining whether breast cancer patients who are close their 70th birthday are recommended standard-of-care radiation or de-escalated treatment is whether they show up a few months before or a few months after that 70th birthday,” commented study author Wesley J. Talcott, MD, of the department of therapeutic radiology at the Yale School of Medicine, New Haven, Conn.
The results show a trend in which radiation therapy is 50% less likely to be prescribed for patients age 70 and older with early-stage breast cancer, even when controlling for population size, patient demographics, and disease specific variables.
This suggests that oncologists are weighing the variable of age too heavily when deciding on adjuvant treatments, the authors suggest.
“In certain circumstances, breast cancer oncology providers are treating age like a binary categorical variable when selecting patients for treatments or diagnostic procedures, rather than the continuous variable that it is,” Dr. Talcott commented.
The study was published online in the International Journal of Radiation Oncology: Biology, Physics.
Approached for comment, Casey Chollet-Lipscomb, MD, radiation oncologist with Tennessee Oncology, Nashville, who was not associated with the study, agreed with its main finding.
“The study helps emphasize the importance of individualized care,” she said. “Increasing age is the most common risk factor for breast cancer, but breast cancer is an incredibly diverse disease. While you can observe trends based on age, every patient is unique, and they can’t be lumped into one bucket and prescribed treatment based on a strict age cutoff.”
The retrospective study included two cohorts of women identified in the National Cancer Data Base (2004-2017) all of whom underwent lumpectomy for early-stage breast cancer. All patients had “strong indications” for adjuvant treatment.
Patients in cohort 1 (n = 160,990) included women with estrogen-receptor negative cancer, tumor size greater than 3 cm, who were determined to be “appropriate” for radiation therapy.
Patients in cohort 2 (n = 394,946) had hormone-receptor positive cancer, tumor size greater than 5 mm, and were considered to be “appropriate” candidates for endocrine therapy.
Multivariable analysis was performed to control for comorbidity burden (measured by the Charlson-Deyo Comorbidity Index), race and ethnicity, insurance status, academic versus non-academic treatment center, median annual income of a patient’s area of residence, distance from the site of treatment, and pathology variables including number of lymph nodes sampled, histologic grade, and genomic risk score.
In cohort 1, radiation was recommended for 90%-92% of patients between the ages of 50-69; this dropped to 81% for those aged 70.
After MVA, it was determined that age difference was an independent predictor for adjuvant radiation recommendation only at age 70 versus 69 (odds ratio, 0.47; 95% confidence interval 0.39-0.57, P < .001).
For cohort 2, year-over-year age difference predicted endocrine therapy recommendation only at the juncture between age 70 versus 69 (OR, 0.86, 95% CI 0.74-0.99, P = .001).
“Our results don’t say that we should be increasing the amount of treatment for patients over the age [of] 70 or decreasing that patient treatment for patients younger than age 70. What we believe is that we need to be assessing physiologic age of our patients when treating patients,” Dr. Talcott said.
“We would do this by looking at not just how many years a patient has been on this Earth but also what their current health status is, how many good quality-of-life years they might have after treatment or without it, and what the patient wants in terms of burden of treatment. This is a much more valuable way to approach the allocation of treatments than using age alone,” he added.
Both Dr. Talcott and Dr. Chollet-Lipscomb agreed that a limitation of the study was a lack of data on how physicians decided on a specific treatment in each individual case, but they agree that even without this information the results were “significant.”
Dr. Chollet-Lipscomb also highlighted the factors other than age she would use to determine the best adjuvant treatment for a patient with early stage breast cancer, including the individual features of the tumor, how aggressive it looks under the microscope, what the receptor status is, and a patient’s overall performance status and comorbidities.
Dr. Talcott and Dr. Chollet-Lipscomb report no relevant financial relationships. The authors had no acknowledgement of research support for this study.
A version of this article first appeared on Medscape.com.
FROM THE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY: BIOLOGY, PHYSICS
Maintenance therapies boost MM survival rates
These results, published in The Lancet Oncology, are not yet practice-changing, but they add to a growing body of evidence supporting this approach.
“Bearing in mind that ATLAS trial data come from unplanned interim analysis, we found that the benefit of combination therapy (KRd) is clearly seen, especially for standard risk patients. We think that, since there are no vast differences in toxicities, there is quite convincing data for considering KRd maintenance for the post autologous stem cell transplantation treatment of MM patients,” ATLAS study coauthor Andrzej Jakubowiak, MD, professor of medicine at the University of Chicago, said in an interview.
Among patients receiving KRd (n = 93), median PFS was 59 months (95% confidence interval) compared with 41 months in the R group (hazard ratio, 0.51, P = .012). These results come from data collected between 2016 and 2020, from 12 academic and clinical centers in the United States and Poland. The cohort included 180 adults randomly assigned to each study arm, (47% were female, median age 59 years) The most common adverse events were neutropenia 48% vs. 60%, thrombocytopenia 13% vs. 7%, and lower respiratory tract infections 8% vs. 1% in the KRd and R groups, respectively. Serious adverse events were reported in 30% of patients in the KRd arm (including one death due to severe pneumonia) and 22% in the R group.
“As expected, there is a slightly higher toxicity in the KRd arm but mostly low-grade events occurred. We believe in KRd maintenance because it provides a longer remission for a relatively small price. The longer a patient is in remission, the better chance that, if relapse does occur, there will be more therapeutic options available to return to remission,” said Dr. Jakubowiak.
Although all patients in the trial received stem cell therapy, the induction therapies were varied.
“We designed the study similarly to the CALGB maintenance trial, one of the key phase 3 trials leading to the approval of lenalidomide as post transplantation maintenance. With so many changes currently occurring MM therapies, having a fixed induction can be its own limitation. Importantly, with our study design we found that all comers may benefit from KRd maintenance,” he said.
It is important to note that KRd treatment occurred for 36 cycles unless a patient withdrew, died, or achieved minimal residual disease (MRD) status.
“Per study design, the duration of KRd treatment was shortened to eight cycles for patients without high-risk cytogenetics who achieved MRD-negativity after cycle six. For these patients, treatment was converted from KRd to R maintenance as of cycle nine. Despite treatment deescalation, this subset of patients (44% of all KRd patients) contributed strongly to KRd PFS. While this approach will need to be validated in a randomized setting, the results provide a proof of concept that if you achieve MRD-negative status and have standard risk cytogenetics, you don’t have to go on a long KRd treatment,” said Dr. Jakubowiak.
Urvi Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, noted the importance of the study as “the first randomized phase-3 trial suggesting progression free survival superiority of an alternative maintenance therapy to lenalidomide alone.”
Dr. Shah did have concerns about the applicability of the study, especially regarding the use of varied induction regimens, saying, “Only 11%-13% of patients in this study got lenalidomide during induction and 4%-6% got carfilzomib induction. Therefore, most patients were getting new drugs during maintenance different from their induction agents, which has the downside of leaving fewer options for patients when they relapse.”
Asked about these concerns, Dr. Jakubowiak responded, “Our team’s perspective is to ‘buy’ the longest remission possible using the most effective available treatment strategy. If we do this, there is a good chance that when the patient relapses, we will have availability of new drugs.”
He added the caveat: “There’s a small proportion of patients who will be progressing while on treatment and will be potentially more challenging to treat if already given KRd. It has been proposed that KRd maintenance might be primarily considered for patients with high-risk cytogenetics. However, at this interim analysis, there were not enough events in high-risk patients to comment on KRd’s usefulness as a maintenance therapy in this population.”
The KRd arm of the ATLAS trial had a high dropout-rate for reasons other than toxicity and death, but “because consent for collecting data was discontinued, we can’t really dig deeper into explaining why they dropped out, but half of the patients who discontinued in the KRd arm did so after already completing KRd treatment and were already on R maintenance. Once taking this into consideration, the dropout rates in both arms are similar, and the data does not appear skewed,” said Dr. Jakubowiak.
In conclusion, Dr. Jakubowiak noted that the phase-2 FORTE trial, also published recently in The Lancet Oncology, provides supportive data for maintenance therapy with KR versus K.
“It is quite important that the results of both trials be presented to public so that people know that KR or KRd could be reasonably considered for posttransplant maintenance,” he said.
Dr. Shah opined that as yet, the results of neither study were practice changing for maintenance therapy in the United States. She said she would consider using KR maintenance for select patients with high-risk myeloma who received these drugs as induction therapy and where there was concern about early progression, given that this aggressive treatment allows for a longer time in remission.
Dr. Shah noted that in these trials, overall survival data on dual maintenance is still being awaited, and that those results would be important when considering whether to switch patients to a more expensive, toxic, and involved therapy that required regular infusion visits for maintenance.
What Dr. Shah found the most groundbreaking and applicable aspect of the study was that “in the ATLAS trial, they’re adapting treatments to disease response, and if patients achieve MRD negativity, which we know is the best kind of response, therapy was deescalated to lenalidomide single agent. I think this is something that we will see more of in newer study designs and this will help individualize patient treatments to their response.”
Dr. Jakubowiak disclosed consulting fees and honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gracell, GlaxoSmithKline, Janssen, and Sanofi-Aventis. Dr. Shah disclosed ties with Sanofi, Bristol Myers Squibb and Janssen.
These results, published in The Lancet Oncology, are not yet practice-changing, but they add to a growing body of evidence supporting this approach.
“Bearing in mind that ATLAS trial data come from unplanned interim analysis, we found that the benefit of combination therapy (KRd) is clearly seen, especially for standard risk patients. We think that, since there are no vast differences in toxicities, there is quite convincing data for considering KRd maintenance for the post autologous stem cell transplantation treatment of MM patients,” ATLAS study coauthor Andrzej Jakubowiak, MD, professor of medicine at the University of Chicago, said in an interview.
Among patients receiving KRd (n = 93), median PFS was 59 months (95% confidence interval) compared with 41 months in the R group (hazard ratio, 0.51, P = .012). These results come from data collected between 2016 and 2020, from 12 academic and clinical centers in the United States and Poland. The cohort included 180 adults randomly assigned to each study arm, (47% were female, median age 59 years) The most common adverse events were neutropenia 48% vs. 60%, thrombocytopenia 13% vs. 7%, and lower respiratory tract infections 8% vs. 1% in the KRd and R groups, respectively. Serious adverse events were reported in 30% of patients in the KRd arm (including one death due to severe pneumonia) and 22% in the R group.
“As expected, there is a slightly higher toxicity in the KRd arm but mostly low-grade events occurred. We believe in KRd maintenance because it provides a longer remission for a relatively small price. The longer a patient is in remission, the better chance that, if relapse does occur, there will be more therapeutic options available to return to remission,” said Dr. Jakubowiak.
Although all patients in the trial received stem cell therapy, the induction therapies were varied.
“We designed the study similarly to the CALGB maintenance trial, one of the key phase 3 trials leading to the approval of lenalidomide as post transplantation maintenance. With so many changes currently occurring MM therapies, having a fixed induction can be its own limitation. Importantly, with our study design we found that all comers may benefit from KRd maintenance,” he said.
It is important to note that KRd treatment occurred for 36 cycles unless a patient withdrew, died, or achieved minimal residual disease (MRD) status.
“Per study design, the duration of KRd treatment was shortened to eight cycles for patients without high-risk cytogenetics who achieved MRD-negativity after cycle six. For these patients, treatment was converted from KRd to R maintenance as of cycle nine. Despite treatment deescalation, this subset of patients (44% of all KRd patients) contributed strongly to KRd PFS. While this approach will need to be validated in a randomized setting, the results provide a proof of concept that if you achieve MRD-negative status and have standard risk cytogenetics, you don’t have to go on a long KRd treatment,” said Dr. Jakubowiak.
Urvi Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, noted the importance of the study as “the first randomized phase-3 trial suggesting progression free survival superiority of an alternative maintenance therapy to lenalidomide alone.”
Dr. Shah did have concerns about the applicability of the study, especially regarding the use of varied induction regimens, saying, “Only 11%-13% of patients in this study got lenalidomide during induction and 4%-6% got carfilzomib induction. Therefore, most patients were getting new drugs during maintenance different from their induction agents, which has the downside of leaving fewer options for patients when they relapse.”
Asked about these concerns, Dr. Jakubowiak responded, “Our team’s perspective is to ‘buy’ the longest remission possible using the most effective available treatment strategy. If we do this, there is a good chance that when the patient relapses, we will have availability of new drugs.”
He added the caveat: “There’s a small proportion of patients who will be progressing while on treatment and will be potentially more challenging to treat if already given KRd. It has been proposed that KRd maintenance might be primarily considered for patients with high-risk cytogenetics. However, at this interim analysis, there were not enough events in high-risk patients to comment on KRd’s usefulness as a maintenance therapy in this population.”
The KRd arm of the ATLAS trial had a high dropout-rate for reasons other than toxicity and death, but “because consent for collecting data was discontinued, we can’t really dig deeper into explaining why they dropped out, but half of the patients who discontinued in the KRd arm did so after already completing KRd treatment and were already on R maintenance. Once taking this into consideration, the dropout rates in both arms are similar, and the data does not appear skewed,” said Dr. Jakubowiak.
In conclusion, Dr. Jakubowiak noted that the phase-2 FORTE trial, also published recently in The Lancet Oncology, provides supportive data for maintenance therapy with KR versus K.
“It is quite important that the results of both trials be presented to public so that people know that KR or KRd could be reasonably considered for posttransplant maintenance,” he said.
Dr. Shah opined that as yet, the results of neither study were practice changing for maintenance therapy in the United States. She said she would consider using KR maintenance for select patients with high-risk myeloma who received these drugs as induction therapy and where there was concern about early progression, given that this aggressive treatment allows for a longer time in remission.
Dr. Shah noted that in these trials, overall survival data on dual maintenance is still being awaited, and that those results would be important when considering whether to switch patients to a more expensive, toxic, and involved therapy that required regular infusion visits for maintenance.
What Dr. Shah found the most groundbreaking and applicable aspect of the study was that “in the ATLAS trial, they’re adapting treatments to disease response, and if patients achieve MRD negativity, which we know is the best kind of response, therapy was deescalated to lenalidomide single agent. I think this is something that we will see more of in newer study designs and this will help individualize patient treatments to their response.”
Dr. Jakubowiak disclosed consulting fees and honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gracell, GlaxoSmithKline, Janssen, and Sanofi-Aventis. Dr. Shah disclosed ties with Sanofi, Bristol Myers Squibb and Janssen.
These results, published in The Lancet Oncology, are not yet practice-changing, but they add to a growing body of evidence supporting this approach.
“Bearing in mind that ATLAS trial data come from unplanned interim analysis, we found that the benefit of combination therapy (KRd) is clearly seen, especially for standard risk patients. We think that, since there are no vast differences in toxicities, there is quite convincing data for considering KRd maintenance for the post autologous stem cell transplantation treatment of MM patients,” ATLAS study coauthor Andrzej Jakubowiak, MD, professor of medicine at the University of Chicago, said in an interview.
Among patients receiving KRd (n = 93), median PFS was 59 months (95% confidence interval) compared with 41 months in the R group (hazard ratio, 0.51, P = .012). These results come from data collected between 2016 and 2020, from 12 academic and clinical centers in the United States and Poland. The cohort included 180 adults randomly assigned to each study arm, (47% were female, median age 59 years) The most common adverse events were neutropenia 48% vs. 60%, thrombocytopenia 13% vs. 7%, and lower respiratory tract infections 8% vs. 1% in the KRd and R groups, respectively. Serious adverse events were reported in 30% of patients in the KRd arm (including one death due to severe pneumonia) and 22% in the R group.
“As expected, there is a slightly higher toxicity in the KRd arm but mostly low-grade events occurred. We believe in KRd maintenance because it provides a longer remission for a relatively small price. The longer a patient is in remission, the better chance that, if relapse does occur, there will be more therapeutic options available to return to remission,” said Dr. Jakubowiak.
Although all patients in the trial received stem cell therapy, the induction therapies were varied.
“We designed the study similarly to the CALGB maintenance trial, one of the key phase 3 trials leading to the approval of lenalidomide as post transplantation maintenance. With so many changes currently occurring MM therapies, having a fixed induction can be its own limitation. Importantly, with our study design we found that all comers may benefit from KRd maintenance,” he said.
It is important to note that KRd treatment occurred for 36 cycles unless a patient withdrew, died, or achieved minimal residual disease (MRD) status.
“Per study design, the duration of KRd treatment was shortened to eight cycles for patients without high-risk cytogenetics who achieved MRD-negativity after cycle six. For these patients, treatment was converted from KRd to R maintenance as of cycle nine. Despite treatment deescalation, this subset of patients (44% of all KRd patients) contributed strongly to KRd PFS. While this approach will need to be validated in a randomized setting, the results provide a proof of concept that if you achieve MRD-negative status and have standard risk cytogenetics, you don’t have to go on a long KRd treatment,” said Dr. Jakubowiak.
Urvi Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, noted the importance of the study as “the first randomized phase-3 trial suggesting progression free survival superiority of an alternative maintenance therapy to lenalidomide alone.”
Dr. Shah did have concerns about the applicability of the study, especially regarding the use of varied induction regimens, saying, “Only 11%-13% of patients in this study got lenalidomide during induction and 4%-6% got carfilzomib induction. Therefore, most patients were getting new drugs during maintenance different from their induction agents, which has the downside of leaving fewer options for patients when they relapse.”
Asked about these concerns, Dr. Jakubowiak responded, “Our team’s perspective is to ‘buy’ the longest remission possible using the most effective available treatment strategy. If we do this, there is a good chance that when the patient relapses, we will have availability of new drugs.”
He added the caveat: “There’s a small proportion of patients who will be progressing while on treatment and will be potentially more challenging to treat if already given KRd. It has been proposed that KRd maintenance might be primarily considered for patients with high-risk cytogenetics. However, at this interim analysis, there were not enough events in high-risk patients to comment on KRd’s usefulness as a maintenance therapy in this population.”
The KRd arm of the ATLAS trial had a high dropout-rate for reasons other than toxicity and death, but “because consent for collecting data was discontinued, we can’t really dig deeper into explaining why they dropped out, but half of the patients who discontinued in the KRd arm did so after already completing KRd treatment and were already on R maintenance. Once taking this into consideration, the dropout rates in both arms are similar, and the data does not appear skewed,” said Dr. Jakubowiak.
In conclusion, Dr. Jakubowiak noted that the phase-2 FORTE trial, also published recently in The Lancet Oncology, provides supportive data for maintenance therapy with KR versus K.
“It is quite important that the results of both trials be presented to public so that people know that KR or KRd could be reasonably considered for posttransplant maintenance,” he said.
Dr. Shah opined that as yet, the results of neither study were practice changing for maintenance therapy in the United States. She said she would consider using KR maintenance for select patients with high-risk myeloma who received these drugs as induction therapy and where there was concern about early progression, given that this aggressive treatment allows for a longer time in remission.
Dr. Shah noted that in these trials, overall survival data on dual maintenance is still being awaited, and that those results would be important when considering whether to switch patients to a more expensive, toxic, and involved therapy that required regular infusion visits for maintenance.
What Dr. Shah found the most groundbreaking and applicable aspect of the study was that “in the ATLAS trial, they’re adapting treatments to disease response, and if patients achieve MRD negativity, which we know is the best kind of response, therapy was deescalated to lenalidomide single agent. I think this is something that we will see more of in newer study designs and this will help individualize patient treatments to their response.”
Dr. Jakubowiak disclosed consulting fees and honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gracell, GlaxoSmithKline, Janssen, and Sanofi-Aventis. Dr. Shah disclosed ties with Sanofi, Bristol Myers Squibb and Janssen.