Roxanne Nelson, RN

PARIS – “It’s not just what you give, it’s when you give it,” said the investigator reporting “that the same treatment for resectable melanoma given in a different sequence can generate lower rates of melanoma recurrence.”

Sapna Patel, MD, associate professor of melanoma medical oncology at The University of Texas MD Anderson Cancer Center, Houston, reported the results from the SWOG S1801 trial, which showed that patients with high-risk melanoma who received pembrolizumab both before and after surgery had significantly longer event-free survival than patients who received pembrolizumab after surgery only.

At a median follow-up of almost 15 months, there was a 42% lower rate of recurrence or death.

“Compared to the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma,” Dr. Patel commented.

She suggested that the explanation for the findings was that “inhibiting the PD-1/PD-L1 immune checkpoints before surgery gives an antitumor response at local and distant sites, and this occurs before resection of the tumor bed. This approach tends to leave behind a larger number of anti-tumor T cells ... [and] these T cells can be activated and circulated systematically to recognize and attack micro-metastatic melanoma tumors.”

The findings were presented during a presidential symposium at the European Society for Medical Oncology (ESMO) Congress 2022, Paris.

“This trial provides us with more evidence of when one strategy may be preferred over the other,” commented Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was not involved with the trial.

“Neoadjuvant immunotherapy has elicited impressive complete pathologic responses, which thus far have proven to be associated with a durable response. Neoadjuvant therapy may help identify patients who will respond well to checkpoint inhibitors and allow for de-escalation of therapy,” she told this news organization when approached for comment.

“As with all neoadjuvant therapy, we don’t want the treatment to compromise the outcomes of surgery when the intent is curative, and we once again have evidence that this is not the case when it comes to immune therapy,” she said. However, she added that “we will need further survival data to really change the standard of practice in high-risk melanoma and demonstrate whether there is a superior sequence of therapy and surgery.”

 

Details of the new results

The S1801 clinical trial enrolled 345 participants with stage IIIB through stage IV melanoma considered resectable. The cohort was randomized to receive either upfront surgery followed by 18 doses of pembrolizumab 200 mg every 3 weeks for a total of 18 doses or neoadjuvant therapy with pembrolizumab 200 mg (3 doses) followed by 15 doses of adjuvant pembrolizumab.

The primary endpoint was event-free survival (EFS), defined as the time from randomization to the occurrence of one of the following: disease progression or toxicity that resulted in not receiving surgery, failure to begin adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, or death from any cause.

At a median follow-up of 14.7 months, EFS was significantly higher for patients in the neoadjuvant group, compared with those receiving adjuvant therapy only (HR, 0.58; one-sided log-rank P = .004). A total of 36 participants died in the neoadjuvant and adjuvant groups (14 and 22 patients, extrapolating to a hazard ratio of 0.63; one-sided P = .091).

“With a limited number of events, overall survival is not statistically different at this time,” Dr. Patel said. “Landmark 2-year survival was 72% in the neoadjuvant arm and 49% in the adjuvant arm.”

The authors note that the benefit of neoadjuvant therapy remained consistent across a range of factors, including patient age, sex, performance status, stage of disease, ulceration, and BRAF status. The same proportion of patients in both groups received adjuvant pembrolizumab following surgery.

Rates of adverse events were similar in both groups, and neoadjuvant pembrolizumab did not result in an increase in adverse events related to surgery. In the neoadjuvant group, 28 patients (21%) with submitted pathology reports were noted to have had a complete pathologic response (0% viable tumor) on local review.
 

Questions remain

Invited discussant James Larkin, PhD, FRCP, FMedSci, a clinical researcher at The Royal Marsden Hospital, London, noted that the study had “striking results” and was a landmark trial with a simple but powerful design.

However, he pointed to some questions which need to be addressed in the future. “One important question is what is the optimal duration of neoadjuvant treatment, and can we individualize it?”

Another question is just how much postoperative treatment is really needed and whether pathology help determine that. “Can surgery be safely avoided altogether?” he asked. “Another issue is the need for anti-CTL4 therapy – which patients might benefit from anti-CTL4, in addition to anti-PD-1?”

“And by extension, this paradigm provides a great platform for testing new agents, including combinations in cases where PD-1 is not sufficient to achieve a sufficient response,” said Dr. Larkin. “In the future, trials addressing these questions hand us a major opportunity to individualize and rationally de-escalate treatment.”

Also weighing in on the study, another expert pointed out that neoadjuvant therapy in this setting is already being considered as an option. “The use of immunotherapy before surgery has been reported in some trials such as the OPACIN-neo and PRADO trials,” said Anthony J. Olszanski, RPh, MD, Vice Chair of Research at the Fox Chase Cancer Center, Philadelphia. “Results have been quite exciting and have led the NCCN to list this as a potential option for some patients in the current melanoma guidelines.”

S1801 is funded by the NIH/NCI and in part by MSD through a Cooperative Research and Development Agreement with the NCI. Pembrolizumab (KEYTRUDA) is Merck’s anti-PD-1 therapy. Dr. Patel has declared multiple relationships with industry as noted in the abstract; several co-authors have also made disclosures. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and InstilBio and running trials for them.

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

PARIS – “It’s not just what you give, it’s when you give it,” said the investigator reporting “that the same treatment for resectable melanoma given in a different sequence can generate lower rates of melanoma recurrence.”

Sapna Patel, MD, associate professor of melanoma medical oncology at The University of Texas MD Anderson Cancer Center, Houston, reported the results from the SWOG S1801 trial, which showed that patients with high-risk melanoma who received pembrolizumab both before and after surgery had significantly longer event-free survival than patients who received pembrolizumab after surgery only.

At a median follow-up of almost 15 months, there was a 42% lower rate of recurrence or death.

“Compared to the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma,” Dr. Patel commented.

She suggested that the explanation for the findings was that “inhibiting the PD-1/PD-L1 immune checkpoints before surgery gives an antitumor response at local and distant sites, and this occurs before resection of the tumor bed. This approach tends to leave behind a larger number of anti-tumor T cells ... [and] these T cells can be activated and circulated systematically to recognize and attack micro-metastatic melanoma tumors.”

The findings were presented during a presidential symposium at the European Society for Medical Oncology (ESMO) Congress 2022, Paris.

“This trial provides us with more evidence of when one strategy may be preferred over the other,” commented Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was not involved with the trial.

“Neoadjuvant immunotherapy has elicited impressive complete pathologic responses, which thus far have proven to be associated with a durable response. Neoadjuvant therapy may help identify patients who will respond well to checkpoint inhibitors and allow for de-escalation of therapy,” she told this news organization when approached for comment.

“As with all neoadjuvant therapy, we don’t want the treatment to compromise the outcomes of surgery when the intent is curative, and we once again have evidence that this is not the case when it comes to immune therapy,” she said. However, she added that “we will need further survival data to really change the standard of practice in high-risk melanoma and demonstrate whether there is a superior sequence of therapy and surgery.”

 

Details of the new results

The S1801 clinical trial enrolled 345 participants with stage IIIB through stage IV melanoma considered resectable. The cohort was randomized to receive either upfront surgery followed by 18 doses of pembrolizumab 200 mg every 3 weeks for a total of 18 doses or neoadjuvant therapy with pembrolizumab 200 mg (3 doses) followed by 15 doses of adjuvant pembrolizumab.

The primary endpoint was event-free survival (EFS), defined as the time from randomization to the occurrence of one of the following: disease progression or toxicity that resulted in not receiving surgery, failure to begin adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, or death from any cause.

At a median follow-up of 14.7 months, EFS was significantly higher for patients in the neoadjuvant group, compared with those receiving adjuvant therapy only (HR, 0.58; one-sided log-rank P = .004). A total of 36 participants died in the neoadjuvant and adjuvant groups (14 and 22 patients, extrapolating to a hazard ratio of 0.63; one-sided P = .091).

“With a limited number of events, overall survival is not statistically different at this time,” Dr. Patel said. “Landmark 2-year survival was 72% in the neoadjuvant arm and 49% in the adjuvant arm.”

The authors note that the benefit of neoadjuvant therapy remained consistent across a range of factors, including patient age, sex, performance status, stage of disease, ulceration, and BRAF status. The same proportion of patients in both groups received adjuvant pembrolizumab following surgery.

Rates of adverse events were similar in both groups, and neoadjuvant pembrolizumab did not result in an increase in adverse events related to surgery. In the neoadjuvant group, 28 patients (21%) with submitted pathology reports were noted to have had a complete pathologic response (0% viable tumor) on local review.
 

Questions remain

Invited discussant James Larkin, PhD, FRCP, FMedSci, a clinical researcher at The Royal Marsden Hospital, London, noted that the study had “striking results” and was a landmark trial with a simple but powerful design.

However, he pointed to some questions which need to be addressed in the future. “One important question is what is the optimal duration of neoadjuvant treatment, and can we individualize it?”

Another question is just how much postoperative treatment is really needed and whether pathology help determine that. “Can surgery be safely avoided altogether?” he asked. “Another issue is the need for anti-CTL4 therapy – which patients might benefit from anti-CTL4, in addition to anti-PD-1?”

“And by extension, this paradigm provides a great platform for testing new agents, including combinations in cases where PD-1 is not sufficient to achieve a sufficient response,” said Dr. Larkin. “In the future, trials addressing these questions hand us a major opportunity to individualize and rationally de-escalate treatment.”

Also weighing in on the study, another expert pointed out that neoadjuvant therapy in this setting is already being considered as an option. “The use of immunotherapy before surgery has been reported in some trials such as the OPACIN-neo and PRADO trials,” said Anthony J. Olszanski, RPh, MD, Vice Chair of Research at the Fox Chase Cancer Center, Philadelphia. “Results have been quite exciting and have led the NCCN to list this as a potential option for some patients in the current melanoma guidelines.”

S1801 is funded by the NIH/NCI and in part by MSD through a Cooperative Research and Development Agreement with the NCI. Pembrolizumab (KEYTRUDA) is Merck’s anti-PD-1 therapy. Dr. Patel has declared multiple relationships with industry as noted in the abstract; several co-authors have also made disclosures. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and InstilBio and running trials for them.

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

PARIS – “It’s not just what you give, it’s when you give it,” said the investigator reporting “that the same treatment for resectable melanoma given in a different sequence can generate lower rates of melanoma recurrence.”

Sapna Patel, MD, associate professor of melanoma medical oncology at The University of Texas MD Anderson Cancer Center, Houston, reported the results from the SWOG S1801 trial, which showed that patients with high-risk melanoma who received pembrolizumab both before and after surgery had significantly longer event-free survival than patients who received pembrolizumab after surgery only.

At a median follow-up of almost 15 months, there was a 42% lower rate of recurrence or death.

“Compared to the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma,” Dr. Patel commented.

She suggested that the explanation for the findings was that “inhibiting the PD-1/PD-L1 immune checkpoints before surgery gives an antitumor response at local and distant sites, and this occurs before resection of the tumor bed. This approach tends to leave behind a larger number of anti-tumor T cells ... [and] these T cells can be activated and circulated systematically to recognize and attack micro-metastatic melanoma tumors.”

The findings were presented during a presidential symposium at the European Society for Medical Oncology (ESMO) Congress 2022, Paris.

“This trial provides us with more evidence of when one strategy may be preferred over the other,” commented Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was not involved with the trial.

“Neoadjuvant immunotherapy has elicited impressive complete pathologic responses, which thus far have proven to be associated with a durable response. Neoadjuvant therapy may help identify patients who will respond well to checkpoint inhibitors and allow for de-escalation of therapy,” she told this news organization when approached for comment.

“As with all neoadjuvant therapy, we don’t want the treatment to compromise the outcomes of surgery when the intent is curative, and we once again have evidence that this is not the case when it comes to immune therapy,” she said. However, she added that “we will need further survival data to really change the standard of practice in high-risk melanoma and demonstrate whether there is a superior sequence of therapy and surgery.”

 

Details of the new results

The S1801 clinical trial enrolled 345 participants with stage IIIB through stage IV melanoma considered resectable. The cohort was randomized to receive either upfront surgery followed by 18 doses of pembrolizumab 200 mg every 3 weeks for a total of 18 doses or neoadjuvant therapy with pembrolizumab 200 mg (3 doses) followed by 15 doses of adjuvant pembrolizumab.

The primary endpoint was event-free survival (EFS), defined as the time from randomization to the occurrence of one of the following: disease progression or toxicity that resulted in not receiving surgery, failure to begin adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, or death from any cause.

At a median follow-up of 14.7 months, EFS was significantly higher for patients in the neoadjuvant group, compared with those receiving adjuvant therapy only (HR, 0.58; one-sided log-rank P = .004). A total of 36 participants died in the neoadjuvant and adjuvant groups (14 and 22 patients, extrapolating to a hazard ratio of 0.63; one-sided P = .091).

“With a limited number of events, overall survival is not statistically different at this time,” Dr. Patel said. “Landmark 2-year survival was 72% in the neoadjuvant arm and 49% in the adjuvant arm.”

The authors note that the benefit of neoadjuvant therapy remained consistent across a range of factors, including patient age, sex, performance status, stage of disease, ulceration, and BRAF status. The same proportion of patients in both groups received adjuvant pembrolizumab following surgery.

Rates of adverse events were similar in both groups, and neoadjuvant pembrolizumab did not result in an increase in adverse events related to surgery. In the neoadjuvant group, 28 patients (21%) with submitted pathology reports were noted to have had a complete pathologic response (0% viable tumor) on local review.
 

Questions remain

Invited discussant James Larkin, PhD, FRCP, FMedSci, a clinical researcher at The Royal Marsden Hospital, London, noted that the study had “striking results” and was a landmark trial with a simple but powerful design.

However, he pointed to some questions which need to be addressed in the future. “One important question is what is the optimal duration of neoadjuvant treatment, and can we individualize it?”

Another question is just how much postoperative treatment is really needed and whether pathology help determine that. “Can surgery be safely avoided altogether?” he asked. “Another issue is the need for anti-CTL4 therapy – which patients might benefit from anti-CTL4, in addition to anti-PD-1?”

“And by extension, this paradigm provides a great platform for testing new agents, including combinations in cases where PD-1 is not sufficient to achieve a sufficient response,” said Dr. Larkin. “In the future, trials addressing these questions hand us a major opportunity to individualize and rationally de-escalate treatment.”

Also weighing in on the study, another expert pointed out that neoadjuvant therapy in this setting is already being considered as an option. “The use of immunotherapy before surgery has been reported in some trials such as the OPACIN-neo and PRADO trials,” said Anthony J. Olszanski, RPh, MD, Vice Chair of Research at the Fox Chase Cancer Center, Philadelphia. “Results have been quite exciting and have led the NCCN to list this as a potential option for some patients in the current melanoma guidelines.”

S1801 is funded by the NIH/NCI and in part by MSD through a Cooperative Research and Development Agreement with the NCI. Pembrolizumab (KEYTRUDA) is Merck’s anti-PD-1 therapy. Dr. Patel has declared multiple relationships with industry as noted in the abstract; several co-authors have also made disclosures. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and InstilBio and running trials for them.

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

PARIS – Cell therapies have already had a huge impact on the treatment of blood cancers, but progress in solid tumors has proved more difficult. Now, in a first multicenter randomized trial to compare the two, a novel cell therapy showed a superior outcome to immunotherapy in patients with advanced melanoma.

The cell therapy used in this trial was composed of adoptive tumor infiltrating lymphocytes (TIL), which were made individually for each patient, just as chimeric antigen receptor T cells (CAR T cells) are for patients with blood cancers. However, the process involved is somewhat different, as TILs are made from lymphocytes that have infiltrated the patient’s tumor and are obtained by surgery in the tumor, whereas CAR T cells are made from circulating blood cells. 

The phase 3 trial involved 168 patients with unresectable stage IIIC-4 melanoma and showed that patients who were treated with TILs achieved a significantly improved progression-free survival (PFS) when compared with standard immunotherapy with ipilimumab (Yervoy).

The median PFS was more than doubled to 7.2 months with TILs versus 3.1 months with ipilimumab (hazard ratio, 0.50; P < .001).

“We do think that TIL could possibly become a new treatment option for patients with advanced stage melanoma,” commented lead author John Haanen, MD, PhD, research group leader at the Netherlands Cancer Institute in Amsterdam and a professor in translational immunotherapy of cancer at Leiden (the Netherlands) University Medical Center.  

He presented the findings at a presidential symposium during the European Society for Medical Oncology Annual Congress, Paris.

“The results of this trial may fuel further research of TIL in other cancer types, potentially demonstrating benefit in many other solid tumors and expanding available treatments for patients,” said Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was approached for comment by this news organization and was not involved in the research.

Immune checkpoint inhibitors and targeted therapies have become the standard of care for advanced melanoma and greatly improved patient outcomes, she said. But as about half of patients treated with these agents will not achieve a durable benefit, there remains a need for new treatment options.

“Although immunotherapy can yield impressive long-term responses, a substantial percentage of patients will have no response, or no durable response, to checkpoint inhibitors,” said Dr. Dimitrova. “TIL therapy has proven effectiveness in melanoma. However, no phase III trials have been done to date to compare its effectiveness to a standard of care regimen.”

She noted that these results are consistent with past reports of an approximately 50% response rate with an impressive 20% complete response rate in the TIL group. Data from a phase 2 trial reported last year, for example, showed an objective response rate of 36.4%.

“It will be important to determine the persistence of antitumor activity and whether there are biomarkers that could help with patient selection given the resource intensity of the therapy,” Dr. Dimitrova said. “TIL therapy will likely become a new standard of care in metastatic melanoma refractory to immune checkpoint inhibitors.” 
 

Superior to immunotherapy

In the current study, Dr. Haanen and colleagues randomly assigned 168 patients to TIL or ipilimumab (3 mg/kg every 3 weeks, maximum 4 doses). Patients were stratified for BRAFV600 mutation status, treatment line and center, and the majority (86%) were refractory to anti–PD-1 treatment.

Patients in the TIL group underwent resection of a melanoma lesion (2-3 cm) for the ex vivo outgrowth and expansion of tumor-resident T cells. Before the cultured TILs were infused back into the patients from which they were made, the patient underwent nonmyeloablative, lymphodepleting chemotherapy with cyclophosphamide plus fludarabine that was followed by high-dose interleukin-2.

The study’s primary endpoint was progression-free survival, and secondary endpoints included overall and complete response rate, overall survival, and safety.

At a median follow-up of 33 months, TIL significantly improved progression-free survival, compared with ipilimumab. The overall response rate also favored TIL, compared with ipilimumab (49% vs. 21%), with 20% versus 7% complete responses, respectively.

The median overall survival was 25.8 months for TIL and 18.9 months for ipilimumab (HR, 0.83; P = 0.39).

Grade 3 or higher treatment-related adverse events occurred in all TIL and 57% of ipilimumab patients, although Dr. Haanen noted they were manageable and, in most cases, resolved by the time patients were discharged from the hospital.

“There were no new safety concerns with TIL,” said Dr. Haanen, “And these toxicities are driven by the chemotherapy and interleukin-2 that are part of the TIL regimen. There were no long-term sequelae in patients treated with TIL, and health-related quality of life was higher in patients treated with TIL.”
 

Ultra-personalized

Also commenting on the study, Anthony J. Olszanski, MD, RPh, associate professor and vice chair of clinical research, department of hematology/oncology at Fox Chase Cancer Center, Philadelphia, agreed that the treatment of patients with melanoma who do not respond to or progress after receiving treatment with immunotherapy is “challenging and represents an unmet need.”

“TIL therapy is, in some ways, ultra-personalized therapy, because we harvest immune cells from the patient’s tumor, expand them outside of the body, and then re-infuse them,” he said. “This trial, which randomized patients between TIL versus the CTLA-4 inhibitor, ipilimumab, has shown an impressive progression-free survival and overall response rate benefit and will help establish TIL therapy as a viable treatment strategy for some patients.”

The study was supported by the Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the Dutch Ministry of Health, Stichting Avento, Copenhagen University Hospital, Herlev, the Danish Cancer Society, and Capital Region of Denmark Research Foundation.

Dr. Haanen and several of the co-authors have declared multiple relationships with industry as noted in the abstract. Dr. Olszanski reports participation in advisory boards for BMS, Merck, and Instil Bio, and he reports running trials for them.

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

PARIS – Cell therapies have already had a huge impact on the treatment of blood cancers, but progress in solid tumors has proved more difficult. Now, in a first multicenter randomized trial to compare the two, a novel cell therapy showed a superior outcome to immunotherapy in patients with advanced melanoma.

The cell therapy used in this trial was composed of adoptive tumor infiltrating lymphocytes (TIL), which were made individually for each patient, just as chimeric antigen receptor T cells (CAR T cells) are for patients with blood cancers. However, the process involved is somewhat different, as TILs are made from lymphocytes that have infiltrated the patient’s tumor and are obtained by surgery in the tumor, whereas CAR T cells are made from circulating blood cells. 

The phase 3 trial involved 168 patients with unresectable stage IIIC-4 melanoma and showed that patients who were treated with TILs achieved a significantly improved progression-free survival (PFS) when compared with standard immunotherapy with ipilimumab (Yervoy).

The median PFS was more than doubled to 7.2 months with TILs versus 3.1 months with ipilimumab (hazard ratio, 0.50; P < .001).

“We do think that TIL could possibly become a new treatment option for patients with advanced stage melanoma,” commented lead author John Haanen, MD, PhD, research group leader at the Netherlands Cancer Institute in Amsterdam and a professor in translational immunotherapy of cancer at Leiden (the Netherlands) University Medical Center.  

He presented the findings at a presidential symposium during the European Society for Medical Oncology Annual Congress, Paris.

“The results of this trial may fuel further research of TIL in other cancer types, potentially demonstrating benefit in many other solid tumors and expanding available treatments for patients,” said Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was approached for comment by this news organization and was not involved in the research.

Immune checkpoint inhibitors and targeted therapies have become the standard of care for advanced melanoma and greatly improved patient outcomes, she said. But as about half of patients treated with these agents will not achieve a durable benefit, there remains a need for new treatment options.

“Although immunotherapy can yield impressive long-term responses, a substantial percentage of patients will have no response, or no durable response, to checkpoint inhibitors,” said Dr. Dimitrova. “TIL therapy has proven effectiveness in melanoma. However, no phase III trials have been done to date to compare its effectiveness to a standard of care regimen.”

She noted that these results are consistent with past reports of an approximately 50% response rate with an impressive 20% complete response rate in the TIL group. Data from a phase 2 trial reported last year, for example, showed an objective response rate of 36.4%.

“It will be important to determine the persistence of antitumor activity and whether there are biomarkers that could help with patient selection given the resource intensity of the therapy,” Dr. Dimitrova said. “TIL therapy will likely become a new standard of care in metastatic melanoma refractory to immune checkpoint inhibitors.” 
 

Superior to immunotherapy

In the current study, Dr. Haanen and colleagues randomly assigned 168 patients to TIL or ipilimumab (3 mg/kg every 3 weeks, maximum 4 doses). Patients were stratified for BRAFV600 mutation status, treatment line and center, and the majority (86%) were refractory to anti–PD-1 treatment.

Patients in the TIL group underwent resection of a melanoma lesion (2-3 cm) for the ex vivo outgrowth and expansion of tumor-resident T cells. Before the cultured TILs were infused back into the patients from which they were made, the patient underwent nonmyeloablative, lymphodepleting chemotherapy with cyclophosphamide plus fludarabine that was followed by high-dose interleukin-2.

The study’s primary endpoint was progression-free survival, and secondary endpoints included overall and complete response rate, overall survival, and safety.

At a median follow-up of 33 months, TIL significantly improved progression-free survival, compared with ipilimumab. The overall response rate also favored TIL, compared with ipilimumab (49% vs. 21%), with 20% versus 7% complete responses, respectively.

The median overall survival was 25.8 months for TIL and 18.9 months for ipilimumab (HR, 0.83; P = 0.39).

Grade 3 or higher treatment-related adverse events occurred in all TIL and 57% of ipilimumab patients, although Dr. Haanen noted they were manageable and, in most cases, resolved by the time patients were discharged from the hospital.

“There were no new safety concerns with TIL,” said Dr. Haanen, “And these toxicities are driven by the chemotherapy and interleukin-2 that are part of the TIL regimen. There were no long-term sequelae in patients treated with TIL, and health-related quality of life was higher in patients treated with TIL.”
 

Ultra-personalized

Also commenting on the study, Anthony J. Olszanski, MD, RPh, associate professor and vice chair of clinical research, department of hematology/oncology at Fox Chase Cancer Center, Philadelphia, agreed that the treatment of patients with melanoma who do not respond to or progress after receiving treatment with immunotherapy is “challenging and represents an unmet need.”

“TIL therapy is, in some ways, ultra-personalized therapy, because we harvest immune cells from the patient’s tumor, expand them outside of the body, and then re-infuse them,” he said. “This trial, which randomized patients between TIL versus the CTLA-4 inhibitor, ipilimumab, has shown an impressive progression-free survival and overall response rate benefit and will help establish TIL therapy as a viable treatment strategy for some patients.”

The study was supported by the Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the Dutch Ministry of Health, Stichting Avento, Copenhagen University Hospital, Herlev, the Danish Cancer Society, and Capital Region of Denmark Research Foundation.

Dr. Haanen and several of the co-authors have declared multiple relationships with industry as noted in the abstract. Dr. Olszanski reports participation in advisory boards for BMS, Merck, and Instil Bio, and he reports running trials for them.

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

PARIS – Cell therapies have already had a huge impact on the treatment of blood cancers, but progress in solid tumors has proved more difficult. Now, in a first multicenter randomized trial to compare the two, a novel cell therapy showed a superior outcome to immunotherapy in patients with advanced melanoma.

The cell therapy used in this trial was composed of adoptive tumor infiltrating lymphocytes (TIL), which were made individually for each patient, just as chimeric antigen receptor T cells (CAR T cells) are for patients with blood cancers. However, the process involved is somewhat different, as TILs are made from lymphocytes that have infiltrated the patient’s tumor and are obtained by surgery in the tumor, whereas CAR T cells are made from circulating blood cells. 

The phase 3 trial involved 168 patients with unresectable stage IIIC-4 melanoma and showed that patients who were treated with TILs achieved a significantly improved progression-free survival (PFS) when compared with standard immunotherapy with ipilimumab (Yervoy).

The median PFS was more than doubled to 7.2 months with TILs versus 3.1 months with ipilimumab (hazard ratio, 0.50; P < .001).

“We do think that TIL could possibly become a new treatment option for patients with advanced stage melanoma,” commented lead author John Haanen, MD, PhD, research group leader at the Netherlands Cancer Institute in Amsterdam and a professor in translational immunotherapy of cancer at Leiden (the Netherlands) University Medical Center.  

He presented the findings at a presidential symposium during the European Society for Medical Oncology Annual Congress, Paris.

“The results of this trial may fuel further research of TIL in other cancer types, potentially demonstrating benefit in many other solid tumors and expanding available treatments for patients,” said Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was approached for comment by this news organization and was not involved in the research.

Immune checkpoint inhibitors and targeted therapies have become the standard of care for advanced melanoma and greatly improved patient outcomes, she said. But as about half of patients treated with these agents will not achieve a durable benefit, there remains a need for new treatment options.

“Although immunotherapy can yield impressive long-term responses, a substantial percentage of patients will have no response, or no durable response, to checkpoint inhibitors,” said Dr. Dimitrova. “TIL therapy has proven effectiveness in melanoma. However, no phase III trials have been done to date to compare its effectiveness to a standard of care regimen.”

She noted that these results are consistent with past reports of an approximately 50% response rate with an impressive 20% complete response rate in the TIL group. Data from a phase 2 trial reported last year, for example, showed an objective response rate of 36.4%.

“It will be important to determine the persistence of antitumor activity and whether there are biomarkers that could help with patient selection given the resource intensity of the therapy,” Dr. Dimitrova said. “TIL therapy will likely become a new standard of care in metastatic melanoma refractory to immune checkpoint inhibitors.” 
 

Superior to immunotherapy

In the current study, Dr. Haanen and colleagues randomly assigned 168 patients to TIL or ipilimumab (3 mg/kg every 3 weeks, maximum 4 doses). Patients were stratified for BRAFV600 mutation status, treatment line and center, and the majority (86%) were refractory to anti–PD-1 treatment.

Patients in the TIL group underwent resection of a melanoma lesion (2-3 cm) for the ex vivo outgrowth and expansion of tumor-resident T cells. Before the cultured TILs were infused back into the patients from which they were made, the patient underwent nonmyeloablative, lymphodepleting chemotherapy with cyclophosphamide plus fludarabine that was followed by high-dose interleukin-2.

The study’s primary endpoint was progression-free survival, and secondary endpoints included overall and complete response rate, overall survival, and safety.

At a median follow-up of 33 months, TIL significantly improved progression-free survival, compared with ipilimumab. The overall response rate also favored TIL, compared with ipilimumab (49% vs. 21%), with 20% versus 7% complete responses, respectively.

The median overall survival was 25.8 months for TIL and 18.9 months for ipilimumab (HR, 0.83; P = 0.39).

Grade 3 or higher treatment-related adverse events occurred in all TIL and 57% of ipilimumab patients, although Dr. Haanen noted they were manageable and, in most cases, resolved by the time patients were discharged from the hospital.

“There were no new safety concerns with TIL,” said Dr. Haanen, “And these toxicities are driven by the chemotherapy and interleukin-2 that are part of the TIL regimen. There were no long-term sequelae in patients treated with TIL, and health-related quality of life was higher in patients treated with TIL.”
 

Ultra-personalized

Also commenting on the study, Anthony J. Olszanski, MD, RPh, associate professor and vice chair of clinical research, department of hematology/oncology at Fox Chase Cancer Center, Philadelphia, agreed that the treatment of patients with melanoma who do not respond to or progress after receiving treatment with immunotherapy is “challenging and represents an unmet need.”

“TIL therapy is, in some ways, ultra-personalized therapy, because we harvest immune cells from the patient’s tumor, expand them outside of the body, and then re-infuse them,” he said. “This trial, which randomized patients between TIL versus the CTLA-4 inhibitor, ipilimumab, has shown an impressive progression-free survival and overall response rate benefit and will help establish TIL therapy as a viable treatment strategy for some patients.”

The study was supported by the Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the Dutch Ministry of Health, Stichting Avento, Copenhagen University Hospital, Herlev, the Danish Cancer Society, and Capital Region of Denmark Research Foundation.

Dr. Haanen and several of the co-authors have declared multiple relationships with industry as noted in the abstract. Dr. Olszanski reports participation in advisory boards for BMS, Merck, and Instil Bio, and he reports running trials for them.

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

Knee and shoulder pain are common complaints for patients in the primary care office.

But identifying the source of the pain can be complicated,

and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.

Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.

The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”

The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.

“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”

Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”

Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.

“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.

Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.

Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.

An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.

An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.

Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”

In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.

Treating knee pain

Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.

Three types of injections also can help:

• Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
• Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
• Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).

The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.  

“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”

He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.

Shoulder pain

The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.

As with knee pain, the same assessment routine largely applies.

First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?

Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.

Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.

As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.

MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.

Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.

Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.

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

Knee and shoulder pain are common complaints for patients in the primary care office.

But identifying the source of the pain can be complicated,

and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.

Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.

The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”

The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.

“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”

Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”

Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.

“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.

Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.

Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.

An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.

An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.

Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”

In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.

Treating knee pain

Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.

Three types of injections also can help:

• Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
• Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
• Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).

The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.  

“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”

He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.

Shoulder pain

The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.

As with knee pain, the same assessment routine largely applies.

First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?

Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.

Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.

As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.

MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.

Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.

Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.

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

Knee and shoulder pain are common complaints for patients in the primary care office.

But identifying the source of the pain can be complicated,

and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.

Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.

The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”

The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.

“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”

Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”

Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.

“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.

Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.

Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.

An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.

An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.

Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”

In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.

Treating knee pain

Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.

Three types of injections also can help:

• Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
• Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
• Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).

The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.  

“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”

He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.

Shoulder pain

The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.

As with knee pain, the same assessment routine largely applies.

First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?

Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.

Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.

As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.

MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.

Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.

Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.

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

As the COVID-19 pandemic enters its third year, the death toll continues to rise and with it, the number of children who may be left without anyone to care for them.

By Oct. 31, 2021, more than 5 million people worldwide had died from COVID-19, and about 5.2 million children had lost a parent or caregiver, according to new research published in the Lancet Child and Adolescent Health.

Of particular note, wrote the authors, was how the number of affected children surged during the latter part of their study period. During the first 14 months of the pandemic (March 1, 2020, to April 30, 2021), 2,737,300 children were affected by COVID-19-related caregiver death. But that number jumped by 90% during the next 6 months, from April 30 to Oct. 31, 2021, to 5,209,000. Essentially, the number of children who were affected nearly doubled, compared with those observed during that first year.

To put these numbers into perspective, study author Charles Nelson, PhD, professor of pediatrics and neuroscience and professor of psychology in the department of psychiatry at Harvard Medical School, Boston, compared it to the HIV/AIDS pandemic. “The current worldwide estimate is now approaching 6 million,” he said. “For HIV, it took 10 years before the number of orphans hit 5 million but for COVID it took 2 years. This should provide some perspective.”

Dr. Nelson pointed out that there are many other differences between the two pandemics. “There was no vaccine for HIV/AIDS, in contrast to the last year or so for COVID, when illness and death could largely be prevented,” he explained. “The politics surrounding HIV-related deaths seemed ‘relatively’ apolitical compared to COVID.”

Another major difference is that children whose parents had HIV were allowed to visit their parents, but for COVID-19, isolation was in place so many children could not see their parents before they died.

There is also more misinformation versus lack of information about COVID-19, compared to HIV/AIDS. “As an example, one young girl who lost her father to COVID was told by her classmates that her father hadn’t really died, he just abandoned the family,” Dr. Nelson said.
 

Minority communities face heaviest loss

A “companion study” was conducted by the Centers for Disease Control and Prevention, which looked at parental/caregiver death just within the United States. During the period between April 1, 2020, through June 30, 2021, the researchers found that more than 140,000 children under the age of 18 years had lost a parent, custodial grandparent, or grandparent caregiver because of COVID-19. In addition, there were significant racial, ethnic, and geographic disparities in COVID-19–associated death of caregivers, and the highest burden of death was observed in the Southern states along the U.S.-Mexican border for Hispanic children, Southeastern states for Black children, and in states with tribal areas for American Indian/Alaska Native populations. Overall, almost two-thirds (65%) of the children who lost a primary caregiver belonged to a racial or ethnic minority.

But as with the international data, the number of affected children has continued to rise since the end of the original study period. “Seth Flaxman, at Imperial College London, has updated the figures as of end of December for the U.S.,” said Dr. Nelson. The 140,000 has increased to 222,718 who lost a primary or secondary caregiver.

In addition, 192,449 lost a primary caregiver, 175,151 lost a parent, and 30,269 lost a secondary caregiver.

The rate, unfortunately, remains disproportionate to minorities. These data do reflect the inequities that have been observed since the beginning of the pandemic, as COVID-19 unequally affected many racial and ethnic minority groups and put them at a higher risk of severe illness and death. “Native Americans are four times more likely than Whites to be orphaned, and Black and Hispanic children 2.5 times more likely,” said Dr. Nelson.

The COVID Collaborative, a diverse group of leading experts from a wide range of disciplines including health, education, and economics, is working to develop consensus recommendations on pandemic-related issues such as vaccination of children who have lost caregivers. In December 2021, they released Hidden Pain: Children Who Lost a Parent or Caretaker to COVID-19 and What the Nation Can Do to Help Them, a report providing estimates of the number of children who lost a caregiver and concrete recommendations to support them.

“The death of an adult caregiver is life-altering for any child regardless of the circumstances or cause,” said Dan Treglia, PhD, associate professor of practice at the University of Pennsylvania, Philadelphia, and a contributor to Hidden Pain. “Traumatic grief is more common in sudden deaths like accidents where support systems are unable to mobilize in anticipation of the death and COVID-19 patients who die are typically in the hospital for barely a week before they pass.”

This suggests that responses to COVID-19 deaths may be more typical of sudden deaths than those of chronic illness such as cancer, he noted, adding that the pandemic has hindered the systems that children and their caregivers would normally rely on for support.

“Social distancing, for example, has limited informal community relationships critical for emotional health and in the current National Emergency in Children’s Mental Health, as noted by the American Academy of Pediatrics, among others, formal community-based and clinical services are overwhelmed,” said Dr. Treglia.

The authors of Hidden Pain note that the children most likely to lose a parent or other caregiver are generally the most likely to have faced “significant previous adversities that hinder their ability to successfully adapt to new experiences of adversity or trauma.” Studies have now revealed the magnitude of COVID-19–associated parent and caregiver death, and Dr. Treglia pointed out that action is needed from federal, state, and local policymakers to help children who have lost a caregiver to COVID-19.
 

Solutions needed now

“Their whole world has collapsed around them, as they have lost a provider of love, affection, developmental support, and in many cases a provider of critical financial support,” he said. “The federal government has an unparalleled ability to direct resources and attention and shape policy at lower levels of government, and its leadership is critical if we want to ensure care for COVID-bereaved children in all corners of the country.”

At least one state thus far is moving toward legislation to help this population. In California, a state with a high number of children who have lost a caregiver, the Hope, Opportunity, Perseverance, and Empowerment (HOPE) for Children Act has been introduced into the state legislature. If passed into law, children who lost a parent or caregiver to COVID-19 and are in the state’s foster care system or a low-income household would be eligible for a state-funded trust fund.

But while this is a start, the consequences of caregiver loss go far beyond the economics, and can include depression, PTSD, substance use disorder, lower levels of educational attainment, and subsequent lower levels of employment. However, most children (90%-95%) will experience a normative course of grief, according to the COVID Collaboration, which can be managed through family and social support systems. Community-based interventions, such as grief camps, peer support groups, or a mentoring program can also be very helpful.

Camp Erin, for example, is a bereavement camp for children aged 6-17 years. It is run by Eluna, a national nonprofit that supports children and families impacted by grief or addiction. “Camp Erin is the largest national bereavement program for children who are grieving the loss of a family member or caregiver, or other significant person in their lives,” said Mary FitzGerald, CEO of Eluna. “Many families needed help with these new dynamics of loss due to COVID.”

Led by bereavement professionals and volunteers, Camp Erin is a weekend experience that combines grief education and emotional support with traditional and fun activities. “It’s a safe environment for children to explore grief, and be with other children who are also grieving,” said Ms. FitzGerald. “There are 33 locations and it’s free of charge.”

Dr. Treglia emphasized the necessity of providing immediate financial assistance through well-established funding streams. “For example, Temporary Assistance to Needy Families, Supplemental Nutritional Assistance Program, and Social Security Survivor’s Benefits are a good start to reinforce their economic stability and keep financial disaster from piling onto their personal tragedy,” he said. “We also need to buttress community-based organizations and schools to ensure they have the resources and grief competence to identify bereaved children and can either provide services directly or refer them to organizations that can.”

He added that the infrastructure and knowledge already exist and “it’s a matter of making strategic investments at the necessary scale.”

As the COVID-19 pandemic enters its third year, the death toll continues to rise and with it, the number of children who may be left without anyone to care for them.

By Oct. 31, 2021, more than 5 million people worldwide had died from COVID-19, and about 5.2 million children had lost a parent or caregiver, according to new research published in the Lancet Child and Adolescent Health.

Of particular note, wrote the authors, was how the number of affected children surged during the latter part of their study period. During the first 14 months of the pandemic (March 1, 2020, to April 30, 2021), 2,737,300 children were affected by COVID-19-related caregiver death. But that number jumped by 90% during the next 6 months, from April 30 to Oct. 31, 2021, to 5,209,000. Essentially, the number of children who were affected nearly doubled, compared with those observed during that first year.

To put these numbers into perspective, study author Charles Nelson, PhD, professor of pediatrics and neuroscience and professor of psychology in the department of psychiatry at Harvard Medical School, Boston, compared it to the HIV/AIDS pandemic. “The current worldwide estimate is now approaching 6 million,” he said. “For HIV, it took 10 years before the number of orphans hit 5 million but for COVID it took 2 years. This should provide some perspective.”

Dr. Nelson pointed out that there are many other differences between the two pandemics. “There was no vaccine for HIV/AIDS, in contrast to the last year or so for COVID, when illness and death could largely be prevented,” he explained. “The politics surrounding HIV-related deaths seemed ‘relatively’ apolitical compared to COVID.”

Another major difference is that children whose parents had HIV were allowed to visit their parents, but for COVID-19, isolation was in place so many children could not see their parents before they died.

There is also more misinformation versus lack of information about COVID-19, compared to HIV/AIDS. “As an example, one young girl who lost her father to COVID was told by her classmates that her father hadn’t really died, he just abandoned the family,” Dr. Nelson said.
 

Minority communities face heaviest loss

A “companion study” was conducted by the Centers for Disease Control and Prevention, which looked at parental/caregiver death just within the United States. During the period between April 1, 2020, through June 30, 2021, the researchers found that more than 140,000 children under the age of 18 years had lost a parent, custodial grandparent, or grandparent caregiver because of COVID-19. In addition, there were significant racial, ethnic, and geographic disparities in COVID-19–associated death of caregivers, and the highest burden of death was observed in the Southern states along the U.S.-Mexican border for Hispanic children, Southeastern states for Black children, and in states with tribal areas for American Indian/Alaska Native populations. Overall, almost two-thirds (65%) of the children who lost a primary caregiver belonged to a racial or ethnic minority.

But as with the international data, the number of affected children has continued to rise since the end of the original study period. “Seth Flaxman, at Imperial College London, has updated the figures as of end of December for the U.S.,” said Dr. Nelson. The 140,000 has increased to 222,718 who lost a primary or secondary caregiver.

In addition, 192,449 lost a primary caregiver, 175,151 lost a parent, and 30,269 lost a secondary caregiver.

The rate, unfortunately, remains disproportionate to minorities. These data do reflect the inequities that have been observed since the beginning of the pandemic, as COVID-19 unequally affected many racial and ethnic minority groups and put them at a higher risk of severe illness and death. “Native Americans are four times more likely than Whites to be orphaned, and Black and Hispanic children 2.5 times more likely,” said Dr. Nelson.

The COVID Collaborative, a diverse group of leading experts from a wide range of disciplines including health, education, and economics, is working to develop consensus recommendations on pandemic-related issues such as vaccination of children who have lost caregivers. In December 2021, they released Hidden Pain: Children Who Lost a Parent or Caretaker to COVID-19 and What the Nation Can Do to Help Them, a report providing estimates of the number of children who lost a caregiver and concrete recommendations to support them.

“The death of an adult caregiver is life-altering for any child regardless of the circumstances or cause,” said Dan Treglia, PhD, associate professor of practice at the University of Pennsylvania, Philadelphia, and a contributor to Hidden Pain. “Traumatic grief is more common in sudden deaths like accidents where support systems are unable to mobilize in anticipation of the death and COVID-19 patients who die are typically in the hospital for barely a week before they pass.”

This suggests that responses to COVID-19 deaths may be more typical of sudden deaths than those of chronic illness such as cancer, he noted, adding that the pandemic has hindered the systems that children and their caregivers would normally rely on for support.

“Social distancing, for example, has limited informal community relationships critical for emotional health and in the current National Emergency in Children’s Mental Health, as noted by the American Academy of Pediatrics, among others, formal community-based and clinical services are overwhelmed,” said Dr. Treglia.

The authors of Hidden Pain note that the children most likely to lose a parent or other caregiver are generally the most likely to have faced “significant previous adversities that hinder their ability to successfully adapt to new experiences of adversity or trauma.” Studies have now revealed the magnitude of COVID-19–associated parent and caregiver death, and Dr. Treglia pointed out that action is needed from federal, state, and local policymakers to help children who have lost a caregiver to COVID-19.
 

Solutions needed now

“Their whole world has collapsed around them, as they have lost a provider of love, affection, developmental support, and in many cases a provider of critical financial support,” he said. “The federal government has an unparalleled ability to direct resources and attention and shape policy at lower levels of government, and its leadership is critical if we want to ensure care for COVID-bereaved children in all corners of the country.”

At least one state thus far is moving toward legislation to help this population. In California, a state with a high number of children who have lost a caregiver, the Hope, Opportunity, Perseverance, and Empowerment (HOPE) for Children Act has been introduced into the state legislature. If passed into law, children who lost a parent or caregiver to COVID-19 and are in the state’s foster care system or a low-income household would be eligible for a state-funded trust fund.

But while this is a start, the consequences of caregiver loss go far beyond the economics, and can include depression, PTSD, substance use disorder, lower levels of educational attainment, and subsequent lower levels of employment. However, most children (90%-95%) will experience a normative course of grief, according to the COVID Collaboration, which can be managed through family and social support systems. Community-based interventions, such as grief camps, peer support groups, or a mentoring program can also be very helpful.

Camp Erin, for example, is a bereavement camp for children aged 6-17 years. It is run by Eluna, a national nonprofit that supports children and families impacted by grief or addiction. “Camp Erin is the largest national bereavement program for children who are grieving the loss of a family member or caregiver, or other significant person in their lives,” said Mary FitzGerald, CEO of Eluna. “Many families needed help with these new dynamics of loss due to COVID.”

Led by bereavement professionals and volunteers, Camp Erin is a weekend experience that combines grief education and emotional support with traditional and fun activities. “It’s a safe environment for children to explore grief, and be with other children who are also grieving,” said Ms. FitzGerald. “There are 33 locations and it’s free of charge.”

Dr. Treglia emphasized the necessity of providing immediate financial assistance through well-established funding streams. “For example, Temporary Assistance to Needy Families, Supplemental Nutritional Assistance Program, and Social Security Survivor’s Benefits are a good start to reinforce their economic stability and keep financial disaster from piling onto their personal tragedy,” he said. “We also need to buttress community-based organizations and schools to ensure they have the resources and grief competence to identify bereaved children and can either provide services directly or refer them to organizations that can.”

He added that the infrastructure and knowledge already exist and “it’s a matter of making strategic investments at the necessary scale.”

As the COVID-19 pandemic enters its third year, the death toll continues to rise and with it, the number of children who may be left without anyone to care for them.

By Oct. 31, 2021, more than 5 million people worldwide had died from COVID-19, and about 5.2 million children had lost a parent or caregiver, according to new research published in the Lancet Child and Adolescent Health.

Of particular note, wrote the authors, was how the number of affected children surged during the latter part of their study period. During the first 14 months of the pandemic (March 1, 2020, to April 30, 2021), 2,737,300 children were affected by COVID-19-related caregiver death. But that number jumped by 90% during the next 6 months, from April 30 to Oct. 31, 2021, to 5,209,000. Essentially, the number of children who were affected nearly doubled, compared with those observed during that first year.

To put these numbers into perspective, study author Charles Nelson, PhD, professor of pediatrics and neuroscience and professor of psychology in the department of psychiatry at Harvard Medical School, Boston, compared it to the HIV/AIDS pandemic. “The current worldwide estimate is now approaching 6 million,” he said. “For HIV, it took 10 years before the number of orphans hit 5 million but for COVID it took 2 years. This should provide some perspective.”

Dr. Nelson pointed out that there are many other differences between the two pandemics. “There was no vaccine for HIV/AIDS, in contrast to the last year or so for COVID, when illness and death could largely be prevented,” he explained. “The politics surrounding HIV-related deaths seemed ‘relatively’ apolitical compared to COVID.”

Another major difference is that children whose parents had HIV were allowed to visit their parents, but for COVID-19, isolation was in place so many children could not see their parents before they died.

There is also more misinformation versus lack of information about COVID-19, compared to HIV/AIDS. “As an example, one young girl who lost her father to COVID was told by her classmates that her father hadn’t really died, he just abandoned the family,” Dr. Nelson said.
 

Minority communities face heaviest loss

A “companion study” was conducted by the Centers for Disease Control and Prevention, which looked at parental/caregiver death just within the United States. During the period between April 1, 2020, through June 30, 2021, the researchers found that more than 140,000 children under the age of 18 years had lost a parent, custodial grandparent, or grandparent caregiver because of COVID-19. In addition, there were significant racial, ethnic, and geographic disparities in COVID-19–associated death of caregivers, and the highest burden of death was observed in the Southern states along the U.S.-Mexican border for Hispanic children, Southeastern states for Black children, and in states with tribal areas for American Indian/Alaska Native populations. Overall, almost two-thirds (65%) of the children who lost a primary caregiver belonged to a racial or ethnic minority.

But as with the international data, the number of affected children has continued to rise since the end of the original study period. “Seth Flaxman, at Imperial College London, has updated the figures as of end of December for the U.S.,” said Dr. Nelson. The 140,000 has increased to 222,718 who lost a primary or secondary caregiver.

In addition, 192,449 lost a primary caregiver, 175,151 lost a parent, and 30,269 lost a secondary caregiver.

The rate, unfortunately, remains disproportionate to minorities. These data do reflect the inequities that have been observed since the beginning of the pandemic, as COVID-19 unequally affected many racial and ethnic minority groups and put them at a higher risk of severe illness and death. “Native Americans are four times more likely than Whites to be orphaned, and Black and Hispanic children 2.5 times more likely,” said Dr. Nelson.

The COVID Collaborative, a diverse group of leading experts from a wide range of disciplines including health, education, and economics, is working to develop consensus recommendations on pandemic-related issues such as vaccination of children who have lost caregivers. In December 2021, they released Hidden Pain: Children Who Lost a Parent or Caretaker to COVID-19 and What the Nation Can Do to Help Them, a report providing estimates of the number of children who lost a caregiver and concrete recommendations to support them.

“The death of an adult caregiver is life-altering for any child regardless of the circumstances or cause,” said Dan Treglia, PhD, associate professor of practice at the University of Pennsylvania, Philadelphia, and a contributor to Hidden Pain. “Traumatic grief is more common in sudden deaths like accidents where support systems are unable to mobilize in anticipation of the death and COVID-19 patients who die are typically in the hospital for barely a week before they pass.”

This suggests that responses to COVID-19 deaths may be more typical of sudden deaths than those of chronic illness such as cancer, he noted, adding that the pandemic has hindered the systems that children and their caregivers would normally rely on for support.

“Social distancing, for example, has limited informal community relationships critical for emotional health and in the current National Emergency in Children’s Mental Health, as noted by the American Academy of Pediatrics, among others, formal community-based and clinical services are overwhelmed,” said Dr. Treglia.

The authors of Hidden Pain note that the children most likely to lose a parent or other caregiver are generally the most likely to have faced “significant previous adversities that hinder their ability to successfully adapt to new experiences of adversity or trauma.” Studies have now revealed the magnitude of COVID-19–associated parent and caregiver death, and Dr. Treglia pointed out that action is needed from federal, state, and local policymakers to help children who have lost a caregiver to COVID-19.
 

Solutions needed now

“Their whole world has collapsed around them, as they have lost a provider of love, affection, developmental support, and in many cases a provider of critical financial support,” he said. “The federal government has an unparalleled ability to direct resources and attention and shape policy at lower levels of government, and its leadership is critical if we want to ensure care for COVID-bereaved children in all corners of the country.”

At least one state thus far is moving toward legislation to help this population. In California, a state with a high number of children who have lost a caregiver, the Hope, Opportunity, Perseverance, and Empowerment (HOPE) for Children Act has been introduced into the state legislature. If passed into law, children who lost a parent or caregiver to COVID-19 and are in the state’s foster care system or a low-income household would be eligible for a state-funded trust fund.

But while this is a start, the consequences of caregiver loss go far beyond the economics, and can include depression, PTSD, substance use disorder, lower levels of educational attainment, and subsequent lower levels of employment. However, most children (90%-95%) will experience a normative course of grief, according to the COVID Collaboration, which can be managed through family and social support systems. Community-based interventions, such as grief camps, peer support groups, or a mentoring program can also be very helpful.

Camp Erin, for example, is a bereavement camp for children aged 6-17 years. It is run by Eluna, a national nonprofit that supports children and families impacted by grief or addiction. “Camp Erin is the largest national bereavement program for children who are grieving the loss of a family member or caregiver, or other significant person in their lives,” said Mary FitzGerald, CEO of Eluna. “Many families needed help with these new dynamics of loss due to COVID.”

Led by bereavement professionals and volunteers, Camp Erin is a weekend experience that combines grief education and emotional support with traditional and fun activities. “It’s a safe environment for children to explore grief, and be with other children who are also grieving,” said Ms. FitzGerald. “There are 33 locations and it’s free of charge.”

Dr. Treglia emphasized the necessity of providing immediate financial assistance through well-established funding streams. “For example, Temporary Assistance to Needy Families, Supplemental Nutritional Assistance Program, and Social Security Survivor’s Benefits are a good start to reinforce their economic stability and keep financial disaster from piling onto their personal tragedy,” he said. “We also need to buttress community-based organizations and schools to ensure they have the resources and grief competence to identify bereaved children and can either provide services directly or refer them to organizations that can.”

He added that the infrastructure and knowledge already exist and “it’s a matter of making strategic investments at the necessary scale.”

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

A new cell therapy will be available in Europe soon for the treatment of certain blood cancers.

At its late January meeting, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended for approval lisocabtagene maraleucel (Breyanzi, Bristol-Myers Squibb). This chimeric antigen receptor T-cell therapy is indicated for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). The indication is for use in patients who have received at least two lines of treatment.

The benefits of lisocabtagene maraleucel, noted the CHMP, are its ability to provide high and durable responses in patients with relapsed or refractory DLBCL, PMBCL, and FL3B. The most common side effects reported are neutropenia, anemia, cytokine release syndrome, fatigue, and thrombocytopenia.

The product is already approved in the United States for the same indication. The Food and Drug Administration’s approval came with a Risk Evaluation and Mitigation Strategy because of the risk for serious adverse events, including cytokine release syndrome.

During development, it was designated as an orphan medicine. The EMA will now review the information available to date to determine if the orphan designation can be maintained.
 

Biosimilar pegfilgrastim

At the same meeting, the committee recommended approval of a biosimilar product for pegfilgrastim (Stimufend, Fresenius Kabi Deutschland), which is used to reduce the duration of neutropenia and the incidence of febrile neutropenia after cytotoxic chemotherapy.

The committee noted that this product has been shown to be highly similar to the reference product Neulasta (pegfilgrastim), which has been available in the EU for 2 decades (authorized in 2002). Data have demonstrated that Stimufend has comparable quality, safety, and efficacy to Neulasta.

Its full indication is to reduce the duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancies, with the exception of chronic myeloid leukemia (CML) and myelodysplastic syndromes.
 

Generic versions of dasatinib

Also recommended for approval were for two generic formulations of dasatinib (Dasatinib Accord and Dasatinib Accordpharma, both from Accord Healthcare) for the treatment of various leukemias.

These are generic versions of dasatinib (Sprycel), which has been available in the European Union since 2006.

The CHMP noted that studies have demonstrated the satisfactory quality of Dasatinib Accord, as well as its bioequivalence to the reference product. This generic is indicated for the treatment of adult patients with Philadelphia chromosome–positive  acute lymphoblastic leukemia with resistance or intolerance to prior therapy and pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy.

Dasatinib Accordpharma has a wider set of indications, which include the treatment of adult patients with newly diagnosed Ph+ CML in the chronic phase; chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL and lymphoid blast CML with resistance or intolerance to prior therapy. In addition, this generic is indicated for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib and newly diagnosed Ph+ ALL in combination with chemotherapy.

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

A new cell therapy will be available in Europe soon for the treatment of certain blood cancers.

At its late January meeting, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended for approval lisocabtagene maraleucel (Breyanzi, Bristol-Myers Squibb). This chimeric antigen receptor T-cell therapy is indicated for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). The indication is for use in patients who have received at least two lines of treatment.

The benefits of lisocabtagene maraleucel, noted the CHMP, are its ability to provide high and durable responses in patients with relapsed or refractory DLBCL, PMBCL, and FL3B. The most common side effects reported are neutropenia, anemia, cytokine release syndrome, fatigue, and thrombocytopenia.

The product is already approved in the United States for the same indication. The Food and Drug Administration’s approval came with a Risk Evaluation and Mitigation Strategy because of the risk for serious adverse events, including cytokine release syndrome.

During development, it was designated as an orphan medicine. The EMA will now review the information available to date to determine if the orphan designation can be maintained.
 

Biosimilar pegfilgrastim

At the same meeting, the committee recommended approval of a biosimilar product for pegfilgrastim (Stimufend, Fresenius Kabi Deutschland), which is used to reduce the duration of neutropenia and the incidence of febrile neutropenia after cytotoxic chemotherapy.

The committee noted that this product has been shown to be highly similar to the reference product Neulasta (pegfilgrastim), which has been available in the EU for 2 decades (authorized in 2002). Data have demonstrated that Stimufend has comparable quality, safety, and efficacy to Neulasta.

Its full indication is to reduce the duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancies, with the exception of chronic myeloid leukemia (CML) and myelodysplastic syndromes.
 

Generic versions of dasatinib

Also recommended for approval were for two generic formulations of dasatinib (Dasatinib Accord and Dasatinib Accordpharma, both from Accord Healthcare) for the treatment of various leukemias.

These are generic versions of dasatinib (Sprycel), which has been available in the European Union since 2006.

The CHMP noted that studies have demonstrated the satisfactory quality of Dasatinib Accord, as well as its bioequivalence to the reference product. This generic is indicated for the treatment of adult patients with Philadelphia chromosome–positive  acute lymphoblastic leukemia with resistance or intolerance to prior therapy and pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy.

Dasatinib Accordpharma has a wider set of indications, which include the treatment of adult patients with newly diagnosed Ph+ CML in the chronic phase; chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL and lymphoid blast CML with resistance or intolerance to prior therapy. In addition, this generic is indicated for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib and newly diagnosed Ph+ ALL in combination with chemotherapy.

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

A new cell therapy will be available in Europe soon for the treatment of certain blood cancers.

At its late January meeting, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended for approval lisocabtagene maraleucel (Breyanzi, Bristol-Myers Squibb). This chimeric antigen receptor T-cell therapy is indicated for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). The indication is for use in patients who have received at least two lines of treatment.

The benefits of lisocabtagene maraleucel, noted the CHMP, are its ability to provide high and durable responses in patients with relapsed or refractory DLBCL, PMBCL, and FL3B. The most common side effects reported are neutropenia, anemia, cytokine release syndrome, fatigue, and thrombocytopenia.

The product is already approved in the United States for the same indication. The Food and Drug Administration’s approval came with a Risk Evaluation and Mitigation Strategy because of the risk for serious adverse events, including cytokine release syndrome.

During development, it was designated as an orphan medicine. The EMA will now review the information available to date to determine if the orphan designation can be maintained.
 

Biosimilar pegfilgrastim

At the same meeting, the committee recommended approval of a biosimilar product for pegfilgrastim (Stimufend, Fresenius Kabi Deutschland), which is used to reduce the duration of neutropenia and the incidence of febrile neutropenia after cytotoxic chemotherapy.

The committee noted that this product has been shown to be highly similar to the reference product Neulasta (pegfilgrastim), which has been available in the EU for 2 decades (authorized in 2002). Data have demonstrated that Stimufend has comparable quality, safety, and efficacy to Neulasta.

Its full indication is to reduce the duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancies, with the exception of chronic myeloid leukemia (CML) and myelodysplastic syndromes.
 

Generic versions of dasatinib

Also recommended for approval were for two generic formulations of dasatinib (Dasatinib Accord and Dasatinib Accordpharma, both from Accord Healthcare) for the treatment of various leukemias.

These are generic versions of dasatinib (Sprycel), which has been available in the European Union since 2006.

The CHMP noted that studies have demonstrated the satisfactory quality of Dasatinib Accord, as well as its bioequivalence to the reference product. This generic is indicated for the treatment of adult patients with Philadelphia chromosome–positive  acute lymphoblastic leukemia with resistance or intolerance to prior therapy and pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy.

Dasatinib Accordpharma has a wider set of indications, which include the treatment of adult patients with newly diagnosed Ph+ CML in the chronic phase; chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL and lymphoid blast CML with resistance or intolerance to prior therapy. In addition, this generic is indicated for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib and newly diagnosed Ph+ ALL in combination with chemotherapy.

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

Patients with chronic low back pain who participated in therapeutic aquatic exercise had superior improvement in function, pain, quality of life, sleep quality, and mental state, compared with those who received physical therapy, in a new study.

“This is the first study to compare the efficacy of therapeutic aquatic exercise and physical therapy modalities in the treatment of chronic low back pain,” senior coauthors Pei-Jie Chen, PhD and Xue-Qiang Wang, PhD, both of the department of sport rehabilitation, Shanghai (China) University of Sport, wrote in JAMA Network Open. “Therapeutic aquatic exercise is a safe treatment for chronic low back pain and most participants who received it were willing to recommend it to other patients with chronic low back pain.”

As compared with individuals in the physical therapy modalities arm, the therapeutic aquatic exercise experienced greater relief of disability at all time points assessed: after the 3-month intervention, at the 6-month follow-up, and at the 12-month follow-up.

Commenting on the study, Linda Girgis, MD, FAAFP, a family physician in private practice in South River, N.J., agreed that aquatic therapy is a great tool for many chronic low back patients. “It helps them get active for one and do things that may exacerbate their symptoms doing the same exercises on land,” noted Dr. Girgis, who also is a clinical assistant professor at Robert Wood Johnson Medical School, New Brunswick.

She pointed out that access to a pool can be a problem. “But I have found a few physical therapy places in my area that do have access to a pool, and I refer appropriate patients there,” added Dr. Girgis, who was not involved with the study. “I have also found it works well for other types of pain, such as knee and hip pain. It is not for everyone but I have seen some patients get great benefit from it when they didn’t get any with traditional physical therapy.”
 

Aquatic therapy was more beneficial

Low back pain is a common condition, and clinical practice guidelines currently recommend therapeutic exercise and physical therapy modalities. Among the modalities that are available, therapeutic aquatic exercise is often prescribed for chronic low back pain, and it is becoming increasingly popular for treatment of chronic low back pain, the authors stated in their paper. The authors noted that water is an ideal environment for conducting an exercise program given its various properties, including buoyancy pressure, density, thermal capacity, and conductivity.

Two previously published systematic reviews have suggested that therapeutic aquatic exercise may be able to reduce the intensity of back pain and improve function in this population. But to date, evidence regarding long-term benefits in patients with chronic low back pain is very limited and there haven’t been any studies comparing the efficacy of therapeutic aquatic exercise and physical therapy modalities for chronic low back pain, according to the authors.

In this study, 113 individuals with chronic low back pain were randomized to either therapeutic aquatic exercise or to physical therapy, with an endpoint of efficacy regarding disability. This was measured using the Roland-Morris Disability Questionnaire.

Scores ranged from 0 to 24, with higher scores indicating more severe disability. Secondary endpoints included pain intensity, quality of life, sleep quality, and recommendation of intervention, and these were rated using various standardized tools.

Those randomized to the therapeutic aquatic exercise group had about an hour of therapy, beginning with a 10-minute active warm-up session to enhance neuromuscular activation, then an exercise session for 40 minutes followed by a 10-minute cooldown.

The physical therapy group received transcutaneous electrical nerve stimulation and infrared ray thermal therapy, also for 60 minutes. Both groups received these interventions twice a week for 3 months.

The overall mean age of the cohort was 31.0 years, and they were almost evenly divided by gender; 54 were men (47.8%), and 59 were women (52.2%).

As compared with the physical therapy group, individuals participating in therapeutic aquatic exercise group showed improvement in disability by an additional −1.77 points (95% confidence interval, −3.02 to −0.51) at the end of the 3-month intervention; at 6 months it was −2.42 points (95% CI, −4.13 to −0.70) and −3.61 points (95% CI, −5.63 to −1.58) at the 12-month follow-up (P < .001 for overall group x time interaction).

Functional improvement did not appear to be significantly affected by confounders that included age, sex, body mass index, low back pain duration, educational level, or pain level.

For secondary outcomes, those in the therapeutic aquatic exercise group demonstrated improvement in the most severe pain by an additional −0.79 points (95% CI, −1.31 to −0.27) after the 3-month intervention, −1.34 points (95% CI, −2.06 to −0.62) at 6 months, and −2.04 points (95% CI, −2.75 to −1.34) at the 12-month follow-up (P < .001 for overall group x time interaction), as compared with the physical therapy group. All pain scores differed significantly between the two groups at every time point.

In addition, individuals in the therapeutic aquatic exercise group showed more improvements on the 36-item Short-form Health Survey (overall group x time interaction, P = .003), Pittsburgh Sleep Quality Index (overall group x time interaction, P = .02), Tampa Scale for Kinesiophobia (overall group x time interaction, P < .001), and Fear-Avoidance Beliefs Questionnaire (physical activity subscale overall group x time interaction, P = .04), as compared with the physical therapy group. These improvements were also not influenced by confounders.

Finally, at the 12-month follow-up point, those in the aquatic therapy group had significantly greater improvements in the number of participants who met the minimal clinically important difference in pain (at least a 2-point improvement on the numeric rating scale).
 

More outside experts’ takes

“The current research evidence does suggest indeed that aquatic exercise therapy is suitable and often better than land exercise, passive relaxation, or other treatments for many people with low back pain,” commented Stelios Psycharakis PhD, senior lecturer in biomechanics, Institute for Sport, Physical Education and Health Sciences, University of Edinburgh.

He also noted that since low back pain is an issue affecting about 80% of all people at some stage of their life, it is “improbable that one could identify a single type of treatment or exercise therapy that would be suitable for every person with this problem.”

Dr. Psycharakis pointed out that there are also some contraindications for aquatic therapy, such as incontinence and skin conditions. “Other than that though, clinicians should definitely consider aquatic exercise therapy when advising people with chronic low back pain,” he said.

Justin M. Lantz, DPT, agreed that the study showed therapeutic aquatic exercise appears to be safe and beneficial in some patients with chronic low back pain, but he also shared limitations of the new research.

“The study has notable limitations as it did not include patients above 65 years old, pain levels were generally low for the subjects involved, and it did not include a treatment group with land therapeutic exercise – so it is difficult to determine if the beneficial effects reported were due to active exercise or because the exercises were performed in water,” said Dr. Lantz, director of the spine physical therapy fellowship program at the University of Southern California, Los Angeles, and an assistant professor of clinical physical therapy.

He also pointed out that, since active exercise has been shown to be beneficial and is advocated in multiple clinical practice guidelines for chronic low back pain, “it would be helpful to determine if the true effects on pain and disability were due to the water environment or the effect of active exercise itself.”

“Due to the significant positive long-term effects and limited adverse events reported, I believe this study supports the use of therapeutic aquatic exercise in select patient populations with chronic low back pain and should be considered as a part of a rehabilitation treatment plan if accessibility is feasible,” Dr. Lantz said.

The authors of the paper, Dr. Girgis, and Dr. Psycharakis had no conflicts of interest. Justin Lantz is a physical therapy consultant to SI-Bone.

Patients with chronic low back pain who participated in therapeutic aquatic exercise had superior improvement in function, pain, quality of life, sleep quality, and mental state, compared with those who received physical therapy, in a new study.

“This is the first study to compare the efficacy of therapeutic aquatic exercise and physical therapy modalities in the treatment of chronic low back pain,” senior coauthors Pei-Jie Chen, PhD and Xue-Qiang Wang, PhD, both of the department of sport rehabilitation, Shanghai (China) University of Sport, wrote in JAMA Network Open. “Therapeutic aquatic exercise is a safe treatment for chronic low back pain and most participants who received it were willing to recommend it to other patients with chronic low back pain.”

As compared with individuals in the physical therapy modalities arm, the therapeutic aquatic exercise experienced greater relief of disability at all time points assessed: after the 3-month intervention, at the 6-month follow-up, and at the 12-month follow-up.

Commenting on the study, Linda Girgis, MD, FAAFP, a family physician in private practice in South River, N.J., agreed that aquatic therapy is a great tool for many chronic low back patients. “It helps them get active for one and do things that may exacerbate their symptoms doing the same exercises on land,” noted Dr. Girgis, who also is a clinical assistant professor at Robert Wood Johnson Medical School, New Brunswick.

She pointed out that access to a pool can be a problem. “But I have found a few physical therapy places in my area that do have access to a pool, and I refer appropriate patients there,” added Dr. Girgis, who was not involved with the study. “I have also found it works well for other types of pain, such as knee and hip pain. It is not for everyone but I have seen some patients get great benefit from it when they didn’t get any with traditional physical therapy.”
 

Aquatic therapy was more beneficial

Low back pain is a common condition, and clinical practice guidelines currently recommend therapeutic exercise and physical therapy modalities. Among the modalities that are available, therapeutic aquatic exercise is often prescribed for chronic low back pain, and it is becoming increasingly popular for treatment of chronic low back pain, the authors stated in their paper. The authors noted that water is an ideal environment for conducting an exercise program given its various properties, including buoyancy pressure, density, thermal capacity, and conductivity.

Two previously published systematic reviews have suggested that therapeutic aquatic exercise may be able to reduce the intensity of back pain and improve function in this population. But to date, evidence regarding long-term benefits in patients with chronic low back pain is very limited and there haven’t been any studies comparing the efficacy of therapeutic aquatic exercise and physical therapy modalities for chronic low back pain, according to the authors.

In this study, 113 individuals with chronic low back pain were randomized to either therapeutic aquatic exercise or to physical therapy, with an endpoint of efficacy regarding disability. This was measured using the Roland-Morris Disability Questionnaire.

Scores ranged from 0 to 24, with higher scores indicating more severe disability. Secondary endpoints included pain intensity, quality of life, sleep quality, and recommendation of intervention, and these were rated using various standardized tools.

Those randomized to the therapeutic aquatic exercise group had about an hour of therapy, beginning with a 10-minute active warm-up session to enhance neuromuscular activation, then an exercise session for 40 minutes followed by a 10-minute cooldown.

The physical therapy group received transcutaneous electrical nerve stimulation and infrared ray thermal therapy, also for 60 minutes. Both groups received these interventions twice a week for 3 months.

The overall mean age of the cohort was 31.0 years, and they were almost evenly divided by gender; 54 were men (47.8%), and 59 were women (52.2%).

As compared with the physical therapy group, individuals participating in therapeutic aquatic exercise group showed improvement in disability by an additional −1.77 points (95% confidence interval, −3.02 to −0.51) at the end of the 3-month intervention; at 6 months it was −2.42 points (95% CI, −4.13 to −0.70) and −3.61 points (95% CI, −5.63 to −1.58) at the 12-month follow-up (P < .001 for overall group x time interaction).

Functional improvement did not appear to be significantly affected by confounders that included age, sex, body mass index, low back pain duration, educational level, or pain level.

For secondary outcomes, those in the therapeutic aquatic exercise group demonstrated improvement in the most severe pain by an additional −0.79 points (95% CI, −1.31 to −0.27) after the 3-month intervention, −1.34 points (95% CI, −2.06 to −0.62) at 6 months, and −2.04 points (95% CI, −2.75 to −1.34) at the 12-month follow-up (P < .001 for overall group x time interaction), as compared with the physical therapy group. All pain scores differed significantly between the two groups at every time point.

In addition, individuals in the therapeutic aquatic exercise group showed more improvements on the 36-item Short-form Health Survey (overall group x time interaction, P = .003), Pittsburgh Sleep Quality Index (overall group x time interaction, P = .02), Tampa Scale for Kinesiophobia (overall group x time interaction, P < .001), and Fear-Avoidance Beliefs Questionnaire (physical activity subscale overall group x time interaction, P = .04), as compared with the physical therapy group. These improvements were also not influenced by confounders.

Finally, at the 12-month follow-up point, those in the aquatic therapy group had significantly greater improvements in the number of participants who met the minimal clinically important difference in pain (at least a 2-point improvement on the numeric rating scale).
 

More outside experts’ takes

“The current research evidence does suggest indeed that aquatic exercise therapy is suitable and often better than land exercise, passive relaxation, or other treatments for many people with low back pain,” commented Stelios Psycharakis PhD, senior lecturer in biomechanics, Institute for Sport, Physical Education and Health Sciences, University of Edinburgh.

He also noted that since low back pain is an issue affecting about 80% of all people at some stage of their life, it is “improbable that one could identify a single type of treatment or exercise therapy that would be suitable for every person with this problem.”

Dr. Psycharakis pointed out that there are also some contraindications for aquatic therapy, such as incontinence and skin conditions. “Other than that though, clinicians should definitely consider aquatic exercise therapy when advising people with chronic low back pain,” he said.

Justin M. Lantz, DPT, agreed that the study showed therapeutic aquatic exercise appears to be safe and beneficial in some patients with chronic low back pain, but he also shared limitations of the new research.

“The study has notable limitations as it did not include patients above 65 years old, pain levels were generally low for the subjects involved, and it did not include a treatment group with land therapeutic exercise – so it is difficult to determine if the beneficial effects reported were due to active exercise or because the exercises were performed in water,” said Dr. Lantz, director of the spine physical therapy fellowship program at the University of Southern California, Los Angeles, and an assistant professor of clinical physical therapy.

He also pointed out that, since active exercise has been shown to be beneficial and is advocated in multiple clinical practice guidelines for chronic low back pain, “it would be helpful to determine if the true effects on pain and disability were due to the water environment or the effect of active exercise itself.”

“Due to the significant positive long-term effects and limited adverse events reported, I believe this study supports the use of therapeutic aquatic exercise in select patient populations with chronic low back pain and should be considered as a part of a rehabilitation treatment plan if accessibility is feasible,” Dr. Lantz said.

The authors of the paper, Dr. Girgis, and Dr. Psycharakis had no conflicts of interest. Justin Lantz is a physical therapy consultant to SI-Bone.

Patients with chronic low back pain who participated in therapeutic aquatic exercise had superior improvement in function, pain, quality of life, sleep quality, and mental state, compared with those who received physical therapy, in a new study.

“This is the first study to compare the efficacy of therapeutic aquatic exercise and physical therapy modalities in the treatment of chronic low back pain,” senior coauthors Pei-Jie Chen, PhD and Xue-Qiang Wang, PhD, both of the department of sport rehabilitation, Shanghai (China) University of Sport, wrote in JAMA Network Open. “Therapeutic aquatic exercise is a safe treatment for chronic low back pain and most participants who received it were willing to recommend it to other patients with chronic low back pain.”

As compared with individuals in the physical therapy modalities arm, the therapeutic aquatic exercise experienced greater relief of disability at all time points assessed: after the 3-month intervention, at the 6-month follow-up, and at the 12-month follow-up.

Commenting on the study, Linda Girgis, MD, FAAFP, a family physician in private practice in South River, N.J., agreed that aquatic therapy is a great tool for many chronic low back patients. “It helps them get active for one and do things that may exacerbate their symptoms doing the same exercises on land,” noted Dr. Girgis, who also is a clinical assistant professor at Robert Wood Johnson Medical School, New Brunswick.

She pointed out that access to a pool can be a problem. “But I have found a few physical therapy places in my area that do have access to a pool, and I refer appropriate patients there,” added Dr. Girgis, who was not involved with the study. “I have also found it works well for other types of pain, such as knee and hip pain. It is not for everyone but I have seen some patients get great benefit from it when they didn’t get any with traditional physical therapy.”
 

Aquatic therapy was more beneficial

Low back pain is a common condition, and clinical practice guidelines currently recommend therapeutic exercise and physical therapy modalities. Among the modalities that are available, therapeutic aquatic exercise is often prescribed for chronic low back pain, and it is becoming increasingly popular for treatment of chronic low back pain, the authors stated in their paper. The authors noted that water is an ideal environment for conducting an exercise program given its various properties, including buoyancy pressure, density, thermal capacity, and conductivity.

Two previously published systematic reviews have suggested that therapeutic aquatic exercise may be able to reduce the intensity of back pain and improve function in this population. But to date, evidence regarding long-term benefits in patients with chronic low back pain is very limited and there haven’t been any studies comparing the efficacy of therapeutic aquatic exercise and physical therapy modalities for chronic low back pain, according to the authors.

In this study, 113 individuals with chronic low back pain were randomized to either therapeutic aquatic exercise or to physical therapy, with an endpoint of efficacy regarding disability. This was measured using the Roland-Morris Disability Questionnaire.

Scores ranged from 0 to 24, with higher scores indicating more severe disability. Secondary endpoints included pain intensity, quality of life, sleep quality, and recommendation of intervention, and these were rated using various standardized tools.

Those randomized to the therapeutic aquatic exercise group had about an hour of therapy, beginning with a 10-minute active warm-up session to enhance neuromuscular activation, then an exercise session for 40 minutes followed by a 10-minute cooldown.

The physical therapy group received transcutaneous electrical nerve stimulation and infrared ray thermal therapy, also for 60 minutes. Both groups received these interventions twice a week for 3 months.

The overall mean age of the cohort was 31.0 years, and they were almost evenly divided by gender; 54 were men (47.8%), and 59 were women (52.2%).

As compared with the physical therapy group, individuals participating in therapeutic aquatic exercise group showed improvement in disability by an additional −1.77 points (95% confidence interval, −3.02 to −0.51) at the end of the 3-month intervention; at 6 months it was −2.42 points (95% CI, −4.13 to −0.70) and −3.61 points (95% CI, −5.63 to −1.58) at the 12-month follow-up (P < .001 for overall group x time interaction).

Functional improvement did not appear to be significantly affected by confounders that included age, sex, body mass index, low back pain duration, educational level, or pain level.

For secondary outcomes, those in the therapeutic aquatic exercise group demonstrated improvement in the most severe pain by an additional −0.79 points (95% CI, −1.31 to −0.27) after the 3-month intervention, −1.34 points (95% CI, −2.06 to −0.62) at 6 months, and −2.04 points (95% CI, −2.75 to −1.34) at the 12-month follow-up (P < .001 for overall group x time interaction), as compared with the physical therapy group. All pain scores differed significantly between the two groups at every time point.

In addition, individuals in the therapeutic aquatic exercise group showed more improvements on the 36-item Short-form Health Survey (overall group x time interaction, P = .003), Pittsburgh Sleep Quality Index (overall group x time interaction, P = .02), Tampa Scale for Kinesiophobia (overall group x time interaction, P < .001), and Fear-Avoidance Beliefs Questionnaire (physical activity subscale overall group x time interaction, P = .04), as compared with the physical therapy group. These improvements were also not influenced by confounders.

Finally, at the 12-month follow-up point, those in the aquatic therapy group had significantly greater improvements in the number of participants who met the minimal clinically important difference in pain (at least a 2-point improvement on the numeric rating scale).
 

More outside experts’ takes

“The current research evidence does suggest indeed that aquatic exercise therapy is suitable and often better than land exercise, passive relaxation, or other treatments for many people with low back pain,” commented Stelios Psycharakis PhD, senior lecturer in biomechanics, Institute for Sport, Physical Education and Health Sciences, University of Edinburgh.

He also noted that since low back pain is an issue affecting about 80% of all people at some stage of their life, it is “improbable that one could identify a single type of treatment or exercise therapy that would be suitable for every person with this problem.”

Dr. Psycharakis pointed out that there are also some contraindications for aquatic therapy, such as incontinence and skin conditions. “Other than that though, clinicians should definitely consider aquatic exercise therapy when advising people with chronic low back pain,” he said.

Justin M. Lantz, DPT, agreed that the study showed therapeutic aquatic exercise appears to be safe and beneficial in some patients with chronic low back pain, but he also shared limitations of the new research.

“The study has notable limitations as it did not include patients above 65 years old, pain levels were generally low for the subjects involved, and it did not include a treatment group with land therapeutic exercise – so it is difficult to determine if the beneficial effects reported were due to active exercise or because the exercises were performed in water,” said Dr. Lantz, director of the spine physical therapy fellowship program at the University of Southern California, Los Angeles, and an assistant professor of clinical physical therapy.

He also pointed out that, since active exercise has been shown to be beneficial and is advocated in multiple clinical practice guidelines for chronic low back pain, “it would be helpful to determine if the true effects on pain and disability were due to the water environment or the effect of active exercise itself.”

“Due to the significant positive long-term effects and limited adverse events reported, I believe this study supports the use of therapeutic aquatic exercise in select patient populations with chronic low back pain and should be considered as a part of a rehabilitation treatment plan if accessibility is feasible,” Dr. Lantz said.

The authors of the paper, Dr. Girgis, and Dr. Psycharakis had no conflicts of interest. Justin Lantz is a physical therapy consultant to SI-Bone.

Axilla swelling, one of the side effects of the initial COVID-19 vaccine series in women, has also materialized with the boosters.

This inflammation is caused by the enlargement of lymph nodes and can show up as an abnormal finding on mammograms and other types of chest scans, causing concern and even the need for additional imaging and follow up, wrote Constance D. Lehman, MD, PhD, and colleagues in an article published in Journal of the American College of Radiology.

Lymph node swelling is a normal immune system reaction to vaccination, and “COVID-19 vaccinations in the arm are a well-documented cause of inflammatory unilateral axillary adenopathy,” noted Dr. Lehman, in an interview. The side effect will occur on the side of the body where the patient received a vaccine, and it is not always noticeable to the woman experiencing it, she said.

“We’re finding that the patients’ bodies are responding to the booster in many ways that are similar to the initial COVID vaccines, with lymph node swelling, muscle aches and pains, headaches, and so on,” said Dr. Lehman, who is chief of breast imaging at the Massachusetts General Hospital, Boston. There have been no real differences in reactions between the Moderna and Pfizer vaccines, she added.

Because axillary lymph node swelling can obscure mammogram results, staff of at least a few imaging centers, including Penn State Breast Center in Hershey, Pa., and Providence Women’s Imaging Center in Torrance, Calif., told this news organization that they are asking women to delay mammogram imaging either 6 weeks or 4-6 weeks after getting a COVID-19 booster.
 

Experts’ suggestions on mammograms, boosters timing

Other experts, including Jessica Leung, MD, acknowledged that vaccine-related reactive adenopathy is seen after the booster dose and provided recommendations for the timing of getting mammograms and the booster with this in mind.

“I would recommend getting the screening mammogram first, which can be followed immediately by vaccination, even on the same day,” said Jessica Leung, MD, a professor of diagnostic radiology at the University of Texas MD Anderson Cancer Center in Houston, Tex.

“If this is not possible from the scheduling perspective, then the patient should consult her health care provider regarding whether it is okay to wait a bit after receiving the vaccine before getting her screening mammogram.”

The answer to that question will likely depend on the time interval since the prior mammogram and the patient’s personal risk factors for developing breast cancer. Dr. Leung noted. “This is all predicated on the assumption that the patient is asymptomatic. If she has any symptoms, for example a palpable breast lump, then she should seek medical attention regardless of timing of vaccination.”

The same holds true for boosters, she said.

She emphasized that careful consideration should be given before delaying the mammogram. “The medical community has a great deal more knowledge at this time than in the early days of COVID-19 vaccination, so we are often able to identify reactive adenopathy related to vaccination. If patients were to delay the mammogram, any reactive adenopathy may persist, on average, for 4-6 weeks.”

Debra Patt, MD, PhD, MBA, executive vice president at Texas Oncology, professor at the University of Texas at Austin, provided a specific example of when a patient should not delay the diagnostic imaging, which is “in the event that there is an abnormal mass in the breast that requires evaluation.”

Providers are now prepared to address these issues, she added.
 

Dr. Lehman’s nuanced recommendations

“It’s easy to get both a mammogram and booster, and just a matter of timing them – so that the reaction doesn’t interfere with the mammography results,” Dr. Lehman said.

But she emphasized that women should not be choosing between their mammograms or a booster. “We are now saying the same thing that we did with the initial vaccine,” said Dr. Lehman. “We don’t want patients delaying their mammograms, and we don’t want them delaying their boosters – both are critical to staying healthy.”

In her center, a model was developed to navigate vaccine-associated adenopathy. While this approach was developed for the primary vaccine series, the same applies for the booster, which is essentially a third dose of the same vaccine, explained Dr. Lehman.

When patients present for mammography, ultrasound, or MRI, the technologist will document their COVID-19 vaccination status (first or second dose or booster), the date it was given, and the location. Adding vaccination documentation to intake forms helps to support appropriate management of patients who undergo imaging after COVID-19 vaccination. Six weeks is used as the cutoff point for defining “recent” vaccination.

For patients who are getting a screening mammography or MRI, and who have no symptoms beyond unilateral axillary adenopathy on the same side of the body where they received the COVID-19 vaccination (given in the arm) within a 6-week period, the following is included in the screening mammography or screening MRI report: “In the specific setting of a patient with documented recent (within the past 6 weeks) COVID-19 vaccination in the ipsilateral arm, axillary adenopathy is a benign imaging finding. No further imaging is indicated at this time. If there is clinical concern that persists more than 6 weeks after the patient received the final vaccine dose, axillary ultrasound is recommended.”

The experts interviewed reported no conflicts of interest.

Axilla swelling, one of the side effects of the initial COVID-19 vaccine series in women, has also materialized with the boosters.

This inflammation is caused by the enlargement of lymph nodes and can show up as an abnormal finding on mammograms and other types of chest scans, causing concern and even the need for additional imaging and follow up, wrote Constance D. Lehman, MD, PhD, and colleagues in an article published in Journal of the American College of Radiology.

Lymph node swelling is a normal immune system reaction to vaccination, and “COVID-19 vaccinations in the arm are a well-documented cause of inflammatory unilateral axillary adenopathy,” noted Dr. Lehman, in an interview. The side effect will occur on the side of the body where the patient received a vaccine, and it is not always noticeable to the woman experiencing it, she said.

“We’re finding that the patients’ bodies are responding to the booster in many ways that are similar to the initial COVID vaccines, with lymph node swelling, muscle aches and pains, headaches, and so on,” said Dr. Lehman, who is chief of breast imaging at the Massachusetts General Hospital, Boston. There have been no real differences in reactions between the Moderna and Pfizer vaccines, she added.

Because axillary lymph node swelling can obscure mammogram results, staff of at least a few imaging centers, including Penn State Breast Center in Hershey, Pa., and Providence Women’s Imaging Center in Torrance, Calif., told this news organization that they are asking women to delay mammogram imaging either 6 weeks or 4-6 weeks after getting a COVID-19 booster.
 

Experts’ suggestions on mammograms, boosters timing

Other experts, including Jessica Leung, MD, acknowledged that vaccine-related reactive adenopathy is seen after the booster dose and provided recommendations for the timing of getting mammograms and the booster with this in mind.

“I would recommend getting the screening mammogram first, which can be followed immediately by vaccination, even on the same day,” said Jessica Leung, MD, a professor of diagnostic radiology at the University of Texas MD Anderson Cancer Center in Houston, Tex.

“If this is not possible from the scheduling perspective, then the patient should consult her health care provider regarding whether it is okay to wait a bit after receiving the vaccine before getting her screening mammogram.”

The answer to that question will likely depend on the time interval since the prior mammogram and the patient’s personal risk factors for developing breast cancer. Dr. Leung noted. “This is all predicated on the assumption that the patient is asymptomatic. If she has any symptoms, for example a palpable breast lump, then she should seek medical attention regardless of timing of vaccination.”

The same holds true for boosters, she said.

She emphasized that careful consideration should be given before delaying the mammogram. “The medical community has a great deal more knowledge at this time than in the early days of COVID-19 vaccination, so we are often able to identify reactive adenopathy related to vaccination. If patients were to delay the mammogram, any reactive adenopathy may persist, on average, for 4-6 weeks.”

Debra Patt, MD, PhD, MBA, executive vice president at Texas Oncology, professor at the University of Texas at Austin, provided a specific example of when a patient should not delay the diagnostic imaging, which is “in the event that there is an abnormal mass in the breast that requires evaluation.”

Providers are now prepared to address these issues, she added.
 

Dr. Lehman’s nuanced recommendations

“It’s easy to get both a mammogram and booster, and just a matter of timing them – so that the reaction doesn’t interfere with the mammography results,” Dr. Lehman said.

But she emphasized that women should not be choosing between their mammograms or a booster. “We are now saying the same thing that we did with the initial vaccine,” said Dr. Lehman. “We don’t want patients delaying their mammograms, and we don’t want them delaying their boosters – both are critical to staying healthy.”

In her center, a model was developed to navigate vaccine-associated adenopathy. While this approach was developed for the primary vaccine series, the same applies for the booster, which is essentially a third dose of the same vaccine, explained Dr. Lehman.

When patients present for mammography, ultrasound, or MRI, the technologist will document their COVID-19 vaccination status (first or second dose or booster), the date it was given, and the location. Adding vaccination documentation to intake forms helps to support appropriate management of patients who undergo imaging after COVID-19 vaccination. Six weeks is used as the cutoff point for defining “recent” vaccination.

For patients who are getting a screening mammography or MRI, and who have no symptoms beyond unilateral axillary adenopathy on the same side of the body where they received the COVID-19 vaccination (given in the arm) within a 6-week period, the following is included in the screening mammography or screening MRI report: “In the specific setting of a patient with documented recent (within the past 6 weeks) COVID-19 vaccination in the ipsilateral arm, axillary adenopathy is a benign imaging finding. No further imaging is indicated at this time. If there is clinical concern that persists more than 6 weeks after the patient received the final vaccine dose, axillary ultrasound is recommended.”

The experts interviewed reported no conflicts of interest.

Axilla swelling, one of the side effects of the initial COVID-19 vaccine series in women, has also materialized with the boosters.

This inflammation is caused by the enlargement of lymph nodes and can show up as an abnormal finding on mammograms and other types of chest scans, causing concern and even the need for additional imaging and follow up, wrote Constance D. Lehman, MD, PhD, and colleagues in an article published in Journal of the American College of Radiology.

Lymph node swelling is a normal immune system reaction to vaccination, and “COVID-19 vaccinations in the arm are a well-documented cause of inflammatory unilateral axillary adenopathy,” noted Dr. Lehman, in an interview. The side effect will occur on the side of the body where the patient received a vaccine, and it is not always noticeable to the woman experiencing it, she said.

“We’re finding that the patients’ bodies are responding to the booster in many ways that are similar to the initial COVID vaccines, with lymph node swelling, muscle aches and pains, headaches, and so on,” said Dr. Lehman, who is chief of breast imaging at the Massachusetts General Hospital, Boston. There have been no real differences in reactions between the Moderna and Pfizer vaccines, she added.

Because axillary lymph node swelling can obscure mammogram results, staff of at least a few imaging centers, including Penn State Breast Center in Hershey, Pa., and Providence Women’s Imaging Center in Torrance, Calif., told this news organization that they are asking women to delay mammogram imaging either 6 weeks or 4-6 weeks after getting a COVID-19 booster.
 

Experts’ suggestions on mammograms, boosters timing

Other experts, including Jessica Leung, MD, acknowledged that vaccine-related reactive adenopathy is seen after the booster dose and provided recommendations for the timing of getting mammograms and the booster with this in mind.

“I would recommend getting the screening mammogram first, which can be followed immediately by vaccination, even on the same day,” said Jessica Leung, MD, a professor of diagnostic radiology at the University of Texas MD Anderson Cancer Center in Houston, Tex.

“If this is not possible from the scheduling perspective, then the patient should consult her health care provider regarding whether it is okay to wait a bit after receiving the vaccine before getting her screening mammogram.”

The answer to that question will likely depend on the time interval since the prior mammogram and the patient’s personal risk factors for developing breast cancer. Dr. Leung noted. “This is all predicated on the assumption that the patient is asymptomatic. If she has any symptoms, for example a palpable breast lump, then she should seek medical attention regardless of timing of vaccination.”

The same holds true for boosters, she said.

She emphasized that careful consideration should be given before delaying the mammogram. “The medical community has a great deal more knowledge at this time than in the early days of COVID-19 vaccination, so we are often able to identify reactive adenopathy related to vaccination. If patients were to delay the mammogram, any reactive adenopathy may persist, on average, for 4-6 weeks.”

Debra Patt, MD, PhD, MBA, executive vice president at Texas Oncology, professor at the University of Texas at Austin, provided a specific example of when a patient should not delay the diagnostic imaging, which is “in the event that there is an abnormal mass in the breast that requires evaluation.”

Providers are now prepared to address these issues, she added.
 

Dr. Lehman’s nuanced recommendations

“It’s easy to get both a mammogram and booster, and just a matter of timing them – so that the reaction doesn’t interfere with the mammography results,” Dr. Lehman said.

But she emphasized that women should not be choosing between their mammograms or a booster. “We are now saying the same thing that we did with the initial vaccine,” said Dr. Lehman. “We don’t want patients delaying their mammograms, and we don’t want them delaying their boosters – both are critical to staying healthy.”

In her center, a model was developed to navigate vaccine-associated adenopathy. While this approach was developed for the primary vaccine series, the same applies for the booster, which is essentially a third dose of the same vaccine, explained Dr. Lehman.

When patients present for mammography, ultrasound, or MRI, the technologist will document their COVID-19 vaccination status (first or second dose or booster), the date it was given, and the location. Adding vaccination documentation to intake forms helps to support appropriate management of patients who undergo imaging after COVID-19 vaccination. Six weeks is used as the cutoff point for defining “recent” vaccination.

For patients who are getting a screening mammography or MRI, and who have no symptoms beyond unilateral axillary adenopathy on the same side of the body where they received the COVID-19 vaccination (given in the arm) within a 6-week period, the following is included in the screening mammography or screening MRI report: “In the specific setting of a patient with documented recent (within the past 6 weeks) COVID-19 vaccination in the ipsilateral arm, axillary adenopathy is a benign imaging finding. No further imaging is indicated at this time. If there is clinical concern that persists more than 6 weeks after the patient received the final vaccine dose, axillary ultrasound is recommended.”

The experts interviewed reported no conflicts of interest.

The Food and Drug Administration has approved combination nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) to be used as first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.

“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
 

Improved overall survival

The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.

Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).

The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.

The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.

Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).

Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.

Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.

The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
 

New standard of care?

The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.

He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved combination nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) to be used as first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.

“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
 

Improved overall survival

The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.

Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).

The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.

The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.

Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).

Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.

Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.

The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
 

New standard of care?

The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.

He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved combination nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) to be used as first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.

“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
 

Improved overall survival

The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.

Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).

The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.

The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.

Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).

Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.

Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.

The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
 

New standard of care?

The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.

He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”

This article first appeared on Medscape.com.