Leukemia, Myelodysplasia, Transplantation

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.

Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.

“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”

She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.

The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.

Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.

“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
 

Black race a risk factor

For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.

To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.

Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”

Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”

However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).

Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
 

Differences in biomarkers

With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.

On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.

“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.

“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
 

Understudied disparities

Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.

“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”

She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”

The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.

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

Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.

Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.

“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”

She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.

The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.

Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.

“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
 

Black race a risk factor

For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.

To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.

Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”

Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”

However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).

Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
 

Differences in biomarkers

With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.

On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.

“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.

“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
 

Understudied disparities

Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.

“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”

She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”

The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.

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

Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.

Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.

“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”

She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.

The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.

Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.

“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
 

Black race a risk factor

For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.

To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.

Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”

Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”

However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).

Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
 

Differences in biomarkers

With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.

On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.

“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.

“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
 

Understudied disparities

Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.

“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”

She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”

The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.

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

Among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE trial, a 1-year disease-free survival (DFS) rate of 95% in those randomized to placebo after 12 cycles of combined ibrutinib plus venetoclax supports a fixed-duration treatment approach, according to William G. Wierda, MD, PhD, University of Texas, MD Anderson Cancer Center, Houston.

Ibrutinib, a once-daily Bruton kinase inhibitor, is the only targeted therapy for first-line treatment of CLL that has demonstrated significant overall survival benefit in randomized phase 3 studies, Dr. Wierda said at the American Society of Hematology annual meeting, held virtually.

Ibrutinib and venetoclax have synergistic and complementary antitumor activity, he noted, through mobilizing and clearing CLL cells from protective niches and disease compartments beyond blood and bone marrow.

Fixed-duration study

CAPTIVATE (PCYC-1142), an international phase 2 study, evaluated first-line treatment with 12 cycles of the ibrutinib/venetoclax combination in MRD and fixed-duration cohorts. The current primary analysis of 1-year DFS from the MRD cohort tested whether the regimen allows for treatment-free remission in the setting of confirmed undetectable MRD (uMRD).

Patients (n = 164, median age 58 years) in the CAPTIVATE study MRD cohort had previously untreated active CLL/SLL requiring treatment per International Workshop on Chronic Lymphocytic Leukemia criteria.

They received 3 cycles of lead-in ibrutinib (420 mg once daily) followed by 12 cycles of ibrutinib (420 mg once daily plus venetoclax ramp-up to 400 mg once daily). Thereafter, in an MRD-guided 1:1 randomization stratified by immunoglobulin heavy chain (IGHV) mutational status, those with confirmed uMRD received either placebo or ibrutinib, and those with uMRD not confirmed received either ibrutinib or ibrutinib plus venetoclax (both open-label).

Among high-risk features in CAPTIVATE subjects, 60% of patients had unmutated IGHV, with del(17p)/TP53 mutation in 20%, del(11Q) in 17%, complex karyotype in 19%, cytopenias in 36%, bulky lymph nodes in 32%, and absolute neutrophil count ≥25x109/L in 76%.
 

Response findings

The ibrutinib lead-in, Dr. Wierda said, reduced tumor lysis syndrome (TLS) risk, shifting 90% of patients with high baseline TLS risk to medium or low-risk categories (from 77 to 51 patients), precluding need for hospitalization with venetoclax initiation.

The rate for best response of uMRD (defined as uMRD over at least 3 cycles in both peripheral blood and bone marrow) in evaluable patients was 75% in peripheral blood (n = 163) and 72% in bone marrow (n = 155).

Confirmed uMRD was achieved in 86/149 (58%), with uMRD not confirmed in 63/149 (uMRD 32% in bone marrow and 48% in peripheral blood). One-year DFS after the further randomization to placebo or ibrutinib in the confirmed uMRD group was 95.3% in the placebo group and 100% in the ibrutinib group (P = .1475). In the uMRD not confirmed group, 30-month progression-free survival (PFS) was 95.2% and 96.7% in the ibrutinib and ibrutinib plus venetoclax groups, respectively. Thirty-month PFS rates in the confirmed uMRD placebo and ibrutinib arms were 95.3% and 100%. “Thirty-month PFS rates were greater than 95% across all randomized arms,” Dr. Wierda stated.

In patients without confirmed uMRD after 12 cycles of combined ibrutinib plus venetoclax, additional randomized treatment led to greater increases in uMRD in the ibrutinib plus venetoclax group than in the ibrutinib alone group (bone marrow additional 10% ibrutinib alone, 34% ibrutinib plus venetoclax; peripheral blood 0% ibrutinib, 19% ibrutinib plus venetoclax).

Adverse events generally decreased after the first 6 months of ibrutinib plus venetoclax treatment, with no new safety signals emerging over time. “There were no safety concerns with this highly active combination of first-line ibrutinib plus venetoclax. It’s an oral, once-daily fixed duration regimen that achieves undetectable MRD in blood or bone marrow in three-fourths of patients after 12 cycles of combined treatment.”

When asked, in a question-and-answer session after his presentation, if the findings were “practice changing,” Dr. Wierda responded: “We need additional data from ongoing studies looking at various combinations of targeted therapy. But this study does clearly show efficacy in terms of depth of remission, and it supports the concept of fixed duration treatment, particularly for those patients who achieved undetectable MRD status.”
 

SOURCE: William G. Wierda, MD, PhD. ASH 2020, Abstract 123.

Among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE trial, a 1-year disease-free survival (DFS) rate of 95% in those randomized to placebo after 12 cycles of combined ibrutinib plus venetoclax supports a fixed-duration treatment approach, according to William G. Wierda, MD, PhD, University of Texas, MD Anderson Cancer Center, Houston.

Ibrutinib, a once-daily Bruton kinase inhibitor, is the only targeted therapy for first-line treatment of CLL that has demonstrated significant overall survival benefit in randomized phase 3 studies, Dr. Wierda said at the American Society of Hematology annual meeting, held virtually.

Ibrutinib and venetoclax have synergistic and complementary antitumor activity, he noted, through mobilizing and clearing CLL cells from protective niches and disease compartments beyond blood and bone marrow.

Fixed-duration study

CAPTIVATE (PCYC-1142), an international phase 2 study, evaluated first-line treatment with 12 cycles of the ibrutinib/venetoclax combination in MRD and fixed-duration cohorts. The current primary analysis of 1-year DFS from the MRD cohort tested whether the regimen allows for treatment-free remission in the setting of confirmed undetectable MRD (uMRD).

Patients (n = 164, median age 58 years) in the CAPTIVATE study MRD cohort had previously untreated active CLL/SLL requiring treatment per International Workshop on Chronic Lymphocytic Leukemia criteria.

They received 3 cycles of lead-in ibrutinib (420 mg once daily) followed by 12 cycles of ibrutinib (420 mg once daily plus venetoclax ramp-up to 400 mg once daily). Thereafter, in an MRD-guided 1:1 randomization stratified by immunoglobulin heavy chain (IGHV) mutational status, those with confirmed uMRD received either placebo or ibrutinib, and those with uMRD not confirmed received either ibrutinib or ibrutinib plus venetoclax (both open-label).

Among high-risk features in CAPTIVATE subjects, 60% of patients had unmutated IGHV, with del(17p)/TP53 mutation in 20%, del(11Q) in 17%, complex karyotype in 19%, cytopenias in 36%, bulky lymph nodes in 32%, and absolute neutrophil count ≥25x109/L in 76%.
 

Response findings

The ibrutinib lead-in, Dr. Wierda said, reduced tumor lysis syndrome (TLS) risk, shifting 90% of patients with high baseline TLS risk to medium or low-risk categories (from 77 to 51 patients), precluding need for hospitalization with venetoclax initiation.

The rate for best response of uMRD (defined as uMRD over at least 3 cycles in both peripheral blood and bone marrow) in evaluable patients was 75% in peripheral blood (n = 163) and 72% in bone marrow (n = 155).

Confirmed uMRD was achieved in 86/149 (58%), with uMRD not confirmed in 63/149 (uMRD 32% in bone marrow and 48% in peripheral blood). One-year DFS after the further randomization to placebo or ibrutinib in the confirmed uMRD group was 95.3% in the placebo group and 100% in the ibrutinib group (P = .1475). In the uMRD not confirmed group, 30-month progression-free survival (PFS) was 95.2% and 96.7% in the ibrutinib and ibrutinib plus venetoclax groups, respectively. Thirty-month PFS rates in the confirmed uMRD placebo and ibrutinib arms were 95.3% and 100%. “Thirty-month PFS rates were greater than 95% across all randomized arms,” Dr. Wierda stated.

In patients without confirmed uMRD after 12 cycles of combined ibrutinib plus venetoclax, additional randomized treatment led to greater increases in uMRD in the ibrutinib plus venetoclax group than in the ibrutinib alone group (bone marrow additional 10% ibrutinib alone, 34% ibrutinib plus venetoclax; peripheral blood 0% ibrutinib, 19% ibrutinib plus venetoclax).

Adverse events generally decreased after the first 6 months of ibrutinib plus venetoclax treatment, with no new safety signals emerging over time. “There were no safety concerns with this highly active combination of first-line ibrutinib plus venetoclax. It’s an oral, once-daily fixed duration regimen that achieves undetectable MRD in blood or bone marrow in three-fourths of patients after 12 cycles of combined treatment.”

When asked, in a question-and-answer session after his presentation, if the findings were “practice changing,” Dr. Wierda responded: “We need additional data from ongoing studies looking at various combinations of targeted therapy. But this study does clearly show efficacy in terms of depth of remission, and it supports the concept of fixed duration treatment, particularly for those patients who achieved undetectable MRD status.”
 

SOURCE: William G. Wierda, MD, PhD. ASH 2020, Abstract 123.

Among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE trial, a 1-year disease-free survival (DFS) rate of 95% in those randomized to placebo after 12 cycles of combined ibrutinib plus venetoclax supports a fixed-duration treatment approach, according to William G. Wierda, MD, PhD, University of Texas, MD Anderson Cancer Center, Houston.

Ibrutinib, a once-daily Bruton kinase inhibitor, is the only targeted therapy for first-line treatment of CLL that has demonstrated significant overall survival benefit in randomized phase 3 studies, Dr. Wierda said at the American Society of Hematology annual meeting, held virtually.

Ibrutinib and venetoclax have synergistic and complementary antitumor activity, he noted, through mobilizing and clearing CLL cells from protective niches and disease compartments beyond blood and bone marrow.

Fixed-duration study

CAPTIVATE (PCYC-1142), an international phase 2 study, evaluated first-line treatment with 12 cycles of the ibrutinib/venetoclax combination in MRD and fixed-duration cohorts. The current primary analysis of 1-year DFS from the MRD cohort tested whether the regimen allows for treatment-free remission in the setting of confirmed undetectable MRD (uMRD).

Patients (n = 164, median age 58 years) in the CAPTIVATE study MRD cohort had previously untreated active CLL/SLL requiring treatment per International Workshop on Chronic Lymphocytic Leukemia criteria.

They received 3 cycles of lead-in ibrutinib (420 mg once daily) followed by 12 cycles of ibrutinib (420 mg once daily plus venetoclax ramp-up to 400 mg once daily). Thereafter, in an MRD-guided 1:1 randomization stratified by immunoglobulin heavy chain (IGHV) mutational status, those with confirmed uMRD received either placebo or ibrutinib, and those with uMRD not confirmed received either ibrutinib or ibrutinib plus venetoclax (both open-label).

Among high-risk features in CAPTIVATE subjects, 60% of patients had unmutated IGHV, with del(17p)/TP53 mutation in 20%, del(11Q) in 17%, complex karyotype in 19%, cytopenias in 36%, bulky lymph nodes in 32%, and absolute neutrophil count ≥25x109/L in 76%.
 

Response findings

The ibrutinib lead-in, Dr. Wierda said, reduced tumor lysis syndrome (TLS) risk, shifting 90% of patients with high baseline TLS risk to medium or low-risk categories (from 77 to 51 patients), precluding need for hospitalization with venetoclax initiation.

The rate for best response of uMRD (defined as uMRD over at least 3 cycles in both peripheral blood and bone marrow) in evaluable patients was 75% in peripheral blood (n = 163) and 72% in bone marrow (n = 155).

Confirmed uMRD was achieved in 86/149 (58%), with uMRD not confirmed in 63/149 (uMRD 32% in bone marrow and 48% in peripheral blood). One-year DFS after the further randomization to placebo or ibrutinib in the confirmed uMRD group was 95.3% in the placebo group and 100% in the ibrutinib group (P = .1475). In the uMRD not confirmed group, 30-month progression-free survival (PFS) was 95.2% and 96.7% in the ibrutinib and ibrutinib plus venetoclax groups, respectively. Thirty-month PFS rates in the confirmed uMRD placebo and ibrutinib arms were 95.3% and 100%. “Thirty-month PFS rates were greater than 95% across all randomized arms,” Dr. Wierda stated.

In patients without confirmed uMRD after 12 cycles of combined ibrutinib plus venetoclax, additional randomized treatment led to greater increases in uMRD in the ibrutinib plus venetoclax group than in the ibrutinib alone group (bone marrow additional 10% ibrutinib alone, 34% ibrutinib plus venetoclax; peripheral blood 0% ibrutinib, 19% ibrutinib plus venetoclax).

Adverse events generally decreased after the first 6 months of ibrutinib plus venetoclax treatment, with no new safety signals emerging over time. “There were no safety concerns with this highly active combination of first-line ibrutinib plus venetoclax. It’s an oral, once-daily fixed duration regimen that achieves undetectable MRD in blood or bone marrow in three-fourths of patients after 12 cycles of combined treatment.”

When asked, in a question-and-answer session after his presentation, if the findings were “practice changing,” Dr. Wierda responded: “We need additional data from ongoing studies looking at various combinations of targeted therapy. But this study does clearly show efficacy in terms of depth of remission, and it supports the concept of fixed duration treatment, particularly for those patients who achieved undetectable MRD status.”
 

SOURCE: William G. Wierda, MD, PhD. ASH 2020, Abstract 123.

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

Risk factors for keratinocyte carcinomas, primarily pigment traits and sun sensitivity, were associated with the risk of developing non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL) in an analysis of 92,097 women in France.

The presence of “many or very many nevi [moles]” was particularly associated with the risk of CLL among individuals in the E3N cohort, according to a report published online in Cancer Medicine. E3N is a prospective cohort of French women aged 40-65 years at inclusion in 1990. Researchers collected cancer data at baseline and every 2-3 years.

Hazard ratios and 95% confidence intervals for associations between patients pigmentary traits and sun exposure and their risk for CLL/NHL were estimated using Cox models, according to study author Louis-Marie Garcin, MD, of the Université Paris-Saclay, Villejuif, and colleagues.
 

Common etiology?

Among the 92,097 women included in the study, 622 incident cases of CLL/NHL were observed over a median of 24-years’ follow-up.

The presence of nevi was associated with CLL/NHL risk. The HR for “many or very many nevi” relative to “no nevi” was 1.56. The association with number of nevi was strongest for the risk of CLL, with an HR for “many or very many nevi” of 3.00 vs. 1.32 for NHL. In addition, the researchers found that women whose skin was highly sensitive to sunburn also had a higher risk of CLL (HR, 1.96), while no increased risk of NHL was observed. All HR values were within their respective 95% confidence intervals.

Relevant characteristics that were found to not be associated with added CLL/NHL risk were skin or hair color, number of freckles, and average daily UV dose during spring and summer in the location of residence at birth or at inclusion.

These observations suggest that CLL in particular may share some constitutional risk factors with keratinocyte cancers, according to the researchers.

“We report an association between nevi frequency and CLL/NHL risk, suggesting a partly common genetic etiology of these tumors. Future research should investigate common pathophysiological pathways that could promote the development of both skin carcinoma and CLL/NHL,” the researchers concluded.

The study was sponsored by the French government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Garcin L-M et al. Cancer Med. 2020. doi: 10.1002/cam4.3586.

Risk factors for keratinocyte carcinomas, primarily pigment traits and sun sensitivity, were associated with the risk of developing non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL) in an analysis of 92,097 women in France.

The presence of “many or very many nevi [moles]” was particularly associated with the risk of CLL among individuals in the E3N cohort, according to a report published online in Cancer Medicine. E3N is a prospective cohort of French women aged 40-65 years at inclusion in 1990. Researchers collected cancer data at baseline and every 2-3 years.

Hazard ratios and 95% confidence intervals for associations between patients pigmentary traits and sun exposure and their risk for CLL/NHL were estimated using Cox models, according to study author Louis-Marie Garcin, MD, of the Université Paris-Saclay, Villejuif, and colleagues.
 

Common etiology?

Among the 92,097 women included in the study, 622 incident cases of CLL/NHL were observed over a median of 24-years’ follow-up.

The presence of nevi was associated with CLL/NHL risk. The HR for “many or very many nevi” relative to “no nevi” was 1.56. The association with number of nevi was strongest for the risk of CLL, with an HR for “many or very many nevi” of 3.00 vs. 1.32 for NHL. In addition, the researchers found that women whose skin was highly sensitive to sunburn also had a higher risk of CLL (HR, 1.96), while no increased risk of NHL was observed. All HR values were within their respective 95% confidence intervals.

Relevant characteristics that were found to not be associated with added CLL/NHL risk were skin or hair color, number of freckles, and average daily UV dose during spring and summer in the location of residence at birth or at inclusion.

These observations suggest that CLL in particular may share some constitutional risk factors with keratinocyte cancers, according to the researchers.

“We report an association between nevi frequency and CLL/NHL risk, suggesting a partly common genetic etiology of these tumors. Future research should investigate common pathophysiological pathways that could promote the development of both skin carcinoma and CLL/NHL,” the researchers concluded.

The study was sponsored by the French government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Garcin L-M et al. Cancer Med. 2020. doi: 10.1002/cam4.3586.

Risk factors for keratinocyte carcinomas, primarily pigment traits and sun sensitivity, were associated with the risk of developing non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL) in an analysis of 92,097 women in France.

The presence of “many or very many nevi [moles]” was particularly associated with the risk of CLL among individuals in the E3N cohort, according to a report published online in Cancer Medicine. E3N is a prospective cohort of French women aged 40-65 years at inclusion in 1990. Researchers collected cancer data at baseline and every 2-3 years.

Hazard ratios and 95% confidence intervals for associations between patients pigmentary traits and sun exposure and their risk for CLL/NHL were estimated using Cox models, according to study author Louis-Marie Garcin, MD, of the Université Paris-Saclay, Villejuif, and colleagues.
 

Common etiology?

Among the 92,097 women included in the study, 622 incident cases of CLL/NHL were observed over a median of 24-years’ follow-up.

The presence of nevi was associated with CLL/NHL risk. The HR for “many or very many nevi” relative to “no nevi” was 1.56. The association with number of nevi was strongest for the risk of CLL, with an HR for “many or very many nevi” of 3.00 vs. 1.32 for NHL. In addition, the researchers found that women whose skin was highly sensitive to sunburn also had a higher risk of CLL (HR, 1.96), while no increased risk of NHL was observed. All HR values were within their respective 95% confidence intervals.

Relevant characteristics that were found to not be associated with added CLL/NHL risk were skin or hair color, number of freckles, and average daily UV dose during spring and summer in the location of residence at birth or at inclusion.

These observations suggest that CLL in particular may share some constitutional risk factors with keratinocyte cancers, according to the researchers.

“We report an association between nevi frequency and CLL/NHL risk, suggesting a partly common genetic etiology of these tumors. Future research should investigate common pathophysiological pathways that could promote the development of both skin carcinoma and CLL/NHL,” the researchers concluded.

The study was sponsored by the French government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Garcin L-M et al. Cancer Med. 2020. doi: 10.1002/cam4.3586.

The days of using chemotherapy to treat Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) may be numbered.

In a phase 2 trial, upfront chemotherapy-free induction/consolidation with the tyrosine kinase inhibitor dasatinib (Sprycel) and the bispecific T-cell engager antibody blinatumomab (Blincyto) yielded high rates of molecular response, “impressive” survival at 18 months, and few toxic effects of grade 3 or higher, say researchers.

With this approach, “60% of adult Ph+ ALL patients, of all ages, can obtain a molecular response, and this percent can increase further with more cycles of blinatumomab,” lead researcher Robin Foà, MD, from Sapienza University of Rome, said in an interview.

“The rates of disease-free survival and overall survival at 18 months are highly favorable, and the protocol is associated with limited toxicity,” Dr. Foà added.

“I see this chemo-free approach becoming a realistic approach for a substantial proportion of adult Ph+ ALL patients, particularly for the older patients, keeping in mind that the incidence of Ph+ ALL increases with age,” Dr. Foà said.

The results of the study were published Oct. 22 in the New England Journal of Medicine.
 

‘Innovative’ and ‘highly successful’

This “innovative” chemotherapy-free approach proved “highly successful” with “surprisingly” few toxic effects, Dieter Hoelzer, MD, PhD, University of Frankfurt (Germany), wrote in a linked editorial.

The Italian GIMEMA LAL2116 D-ALBA trial enrolled 63 adults (median age, 54 years; range, 24-82 years) with newly diagnosed Ph+ ALL. All patients received a glucocorticoid for 31 days beginning 7 days before starting treatment with dasatinib.

Dasatinib (140 mg once daily) induction therapy lasted 85 days. All patients who completed the induction phase received blinatumomab (28 mcg/d) consolidation therapy. Dexamethasone (20 mg) was administered before each blinatumomab cycle. To prevent central nervous system adverse events, levetiracetam (500 mg twice daily) was administered.

All but two patients completed dasatinib induction. One was a 73-year-old woman who withdrew from the trial because of toxic effects after 10 days of dasatinib treatment. She later died of pneumonia. The other was an 82-year-old woman who had a complete hematologic response but left the trial because of pneumonia and pneumonitis.

At the end of the induction phase, 98% of the patients (62 of 63) had a complete hematologic response, including the patient with a complete hematologic response who withdrew; 29% (17 of 59 patients) had a molecular response.

Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. At the end of the second blinatumomab cycle, 60% of the patients (33 of 55 patients) had a molecular response.

The percentage of patients with a molecular response increased further after receiving additional cycles of blinatumomab – to 70% (28 of 40 patients) after the third cycle, 81% (29 of 36 patients) after the fourth cycle, and 72% (21 of 29 patients) after the fifth cycle.

At a median follow-up of 18 months, overall survival was 95%, and disease-free survival was 88%.

There were no significant differences in DFS between patients with p190-kd fusion protein (85%) and those with p210-kd fusion protein (95%). However, DFS was lower in patients with IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both).

ABL1 mutations were present in six patients who had increased minimal residual disease during induction therapy. All these mutations were cleared by blinatumomab.

There were six relapses, of which three were hematologic. One occurred in a patient with a major protocol violation (a delay of more than 2 months in receiving blinatumomab), one occurred after 12 months in the patient who discontinued the trial after receiving dasatinib for 12 days, and one occurred in a patient after the second cycle of blinatumomab.

A total of 21 adverse events of grade 3 or higher were noted. They included cytomegalovirus reactivation or infection in six patients; neutropenia in four patients; persistent fever in two patients; and pleural effusion, pulmonary hypertension, and a neurologic disorder in one patient each.

Of the 24 patients who received a stem-cell allograft, two died, but only one death was related to transplant (4%).

The very low nonrelapse mortality among patients who underwent transplant during remission is “remarkable,” Dr. Hoelzer wrote. It suggests that toxicity from induction chemotherapy puts the patient at risk for toxic effects and death from subsequent stem-cell transplant – “a consequence that is avoided with targeted therapy.”
 

Unanswered questions

“Will the excellent outcomes be preserved with longer follow-up? The answer is probably yes, given that the majority of relapses in ALL occur within the first 1.5 to 2.0 years after the initiation of treatment,” Dr. Hoelzer wrote.

He said other outstanding questions include whether long-term outcomes will differ between patients who undergo transplant and those who do not; whether ABL1 mutations emerge; whether minimal residual disease recurs with longer follow-up; and whether this treatment approach can be used for patients with other subtypes of ALL, such as Ph-negative, B-lineage ALL, or even T-cell ALL.

“If these promising trial results hold, chemotherapy-free induction without the immediate and long-term toxic effects of intensive chemotherapy regimens could also be used in adolescents and, finally, in children. These questions will need to be addressed with longer follow-up and large, prospective trials,” Dr. Hoelzer concluded.

The study was supported by grants from the Italian Association for Cancer Research and Sapienza University of Rome.

A version of this article originally appeared on Medscape.com

The days of using chemotherapy to treat Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) may be numbered.

In a phase 2 trial, upfront chemotherapy-free induction/consolidation with the tyrosine kinase inhibitor dasatinib (Sprycel) and the bispecific T-cell engager antibody blinatumomab (Blincyto) yielded high rates of molecular response, “impressive” survival at 18 months, and few toxic effects of grade 3 or higher, say researchers.

With this approach, “60% of adult Ph+ ALL patients, of all ages, can obtain a molecular response, and this percent can increase further with more cycles of blinatumomab,” lead researcher Robin Foà, MD, from Sapienza University of Rome, said in an interview.

“The rates of disease-free survival and overall survival at 18 months are highly favorable, and the protocol is associated with limited toxicity,” Dr. Foà added.

“I see this chemo-free approach becoming a realistic approach for a substantial proportion of adult Ph+ ALL patients, particularly for the older patients, keeping in mind that the incidence of Ph+ ALL increases with age,” Dr. Foà said.

The results of the study were published Oct. 22 in the New England Journal of Medicine.
 

‘Innovative’ and ‘highly successful’

This “innovative” chemotherapy-free approach proved “highly successful” with “surprisingly” few toxic effects, Dieter Hoelzer, MD, PhD, University of Frankfurt (Germany), wrote in a linked editorial.

The Italian GIMEMA LAL2116 D-ALBA trial enrolled 63 adults (median age, 54 years; range, 24-82 years) with newly diagnosed Ph+ ALL. All patients received a glucocorticoid for 31 days beginning 7 days before starting treatment with dasatinib.

Dasatinib (140 mg once daily) induction therapy lasted 85 days. All patients who completed the induction phase received blinatumomab (28 mcg/d) consolidation therapy. Dexamethasone (20 mg) was administered before each blinatumomab cycle. To prevent central nervous system adverse events, levetiracetam (500 mg twice daily) was administered.

All but two patients completed dasatinib induction. One was a 73-year-old woman who withdrew from the trial because of toxic effects after 10 days of dasatinib treatment. She later died of pneumonia. The other was an 82-year-old woman who had a complete hematologic response but left the trial because of pneumonia and pneumonitis.

At the end of the induction phase, 98% of the patients (62 of 63) had a complete hematologic response, including the patient with a complete hematologic response who withdrew; 29% (17 of 59 patients) had a molecular response.

Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. At the end of the second blinatumomab cycle, 60% of the patients (33 of 55 patients) had a molecular response.

The percentage of patients with a molecular response increased further after receiving additional cycles of blinatumomab – to 70% (28 of 40 patients) after the third cycle, 81% (29 of 36 patients) after the fourth cycle, and 72% (21 of 29 patients) after the fifth cycle.

At a median follow-up of 18 months, overall survival was 95%, and disease-free survival was 88%.

There were no significant differences in DFS between patients with p190-kd fusion protein (85%) and those with p210-kd fusion protein (95%). However, DFS was lower in patients with IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both).

ABL1 mutations were present in six patients who had increased minimal residual disease during induction therapy. All these mutations were cleared by blinatumomab.

There were six relapses, of which three were hematologic. One occurred in a patient with a major protocol violation (a delay of more than 2 months in receiving blinatumomab), one occurred after 12 months in the patient who discontinued the trial after receiving dasatinib for 12 days, and one occurred in a patient after the second cycle of blinatumomab.

A total of 21 adverse events of grade 3 or higher were noted. They included cytomegalovirus reactivation or infection in six patients; neutropenia in four patients; persistent fever in two patients; and pleural effusion, pulmonary hypertension, and a neurologic disorder in one patient each.

Of the 24 patients who received a stem-cell allograft, two died, but only one death was related to transplant (4%).

The very low nonrelapse mortality among patients who underwent transplant during remission is “remarkable,” Dr. Hoelzer wrote. It suggests that toxicity from induction chemotherapy puts the patient at risk for toxic effects and death from subsequent stem-cell transplant – “a consequence that is avoided with targeted therapy.”
 

Unanswered questions

“Will the excellent outcomes be preserved with longer follow-up? The answer is probably yes, given that the majority of relapses in ALL occur within the first 1.5 to 2.0 years after the initiation of treatment,” Dr. Hoelzer wrote.

He said other outstanding questions include whether long-term outcomes will differ between patients who undergo transplant and those who do not; whether ABL1 mutations emerge; whether minimal residual disease recurs with longer follow-up; and whether this treatment approach can be used for patients with other subtypes of ALL, such as Ph-negative, B-lineage ALL, or even T-cell ALL.

“If these promising trial results hold, chemotherapy-free induction without the immediate and long-term toxic effects of intensive chemotherapy regimens could also be used in adolescents and, finally, in children. These questions will need to be addressed with longer follow-up and large, prospective trials,” Dr. Hoelzer concluded.

The study was supported by grants from the Italian Association for Cancer Research and Sapienza University of Rome.

A version of this article originally appeared on Medscape.com

The days of using chemotherapy to treat Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) may be numbered.

In a phase 2 trial, upfront chemotherapy-free induction/consolidation with the tyrosine kinase inhibitor dasatinib (Sprycel) and the bispecific T-cell engager antibody blinatumomab (Blincyto) yielded high rates of molecular response, “impressive” survival at 18 months, and few toxic effects of grade 3 or higher, say researchers.

With this approach, “60% of adult Ph+ ALL patients, of all ages, can obtain a molecular response, and this percent can increase further with more cycles of blinatumomab,” lead researcher Robin Foà, MD, from Sapienza University of Rome, said in an interview.

“The rates of disease-free survival and overall survival at 18 months are highly favorable, and the protocol is associated with limited toxicity,” Dr. Foà added.

“I see this chemo-free approach becoming a realistic approach for a substantial proportion of adult Ph+ ALL patients, particularly for the older patients, keeping in mind that the incidence of Ph+ ALL increases with age,” Dr. Foà said.

The results of the study were published Oct. 22 in the New England Journal of Medicine.
 

‘Innovative’ and ‘highly successful’

This “innovative” chemotherapy-free approach proved “highly successful” with “surprisingly” few toxic effects, Dieter Hoelzer, MD, PhD, University of Frankfurt (Germany), wrote in a linked editorial.

The Italian GIMEMA LAL2116 D-ALBA trial enrolled 63 adults (median age, 54 years; range, 24-82 years) with newly diagnosed Ph+ ALL. All patients received a glucocorticoid for 31 days beginning 7 days before starting treatment with dasatinib.

Dasatinib (140 mg once daily) induction therapy lasted 85 days. All patients who completed the induction phase received blinatumomab (28 mcg/d) consolidation therapy. Dexamethasone (20 mg) was administered before each blinatumomab cycle. To prevent central nervous system adverse events, levetiracetam (500 mg twice daily) was administered.

All but two patients completed dasatinib induction. One was a 73-year-old woman who withdrew from the trial because of toxic effects after 10 days of dasatinib treatment. She later died of pneumonia. The other was an 82-year-old woman who had a complete hematologic response but left the trial because of pneumonia and pneumonitis.

At the end of the induction phase, 98% of the patients (62 of 63) had a complete hematologic response, including the patient with a complete hematologic response who withdrew; 29% (17 of 59 patients) had a molecular response.

Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. At the end of the second blinatumomab cycle, 60% of the patients (33 of 55 patients) had a molecular response.

The percentage of patients with a molecular response increased further after receiving additional cycles of blinatumomab – to 70% (28 of 40 patients) after the third cycle, 81% (29 of 36 patients) after the fourth cycle, and 72% (21 of 29 patients) after the fifth cycle.

At a median follow-up of 18 months, overall survival was 95%, and disease-free survival was 88%.

There were no significant differences in DFS between patients with p190-kd fusion protein (85%) and those with p210-kd fusion protein (95%). However, DFS was lower in patients with IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both).

ABL1 mutations were present in six patients who had increased minimal residual disease during induction therapy. All these mutations were cleared by blinatumomab.

There were six relapses, of which three were hematologic. One occurred in a patient with a major protocol violation (a delay of more than 2 months in receiving blinatumomab), one occurred after 12 months in the patient who discontinued the trial after receiving dasatinib for 12 days, and one occurred in a patient after the second cycle of blinatumomab.

A total of 21 adverse events of grade 3 or higher were noted. They included cytomegalovirus reactivation or infection in six patients; neutropenia in four patients; persistent fever in two patients; and pleural effusion, pulmonary hypertension, and a neurologic disorder in one patient each.

Of the 24 patients who received a stem-cell allograft, two died, but only one death was related to transplant (4%).

The very low nonrelapse mortality among patients who underwent transplant during remission is “remarkable,” Dr. Hoelzer wrote. It suggests that toxicity from induction chemotherapy puts the patient at risk for toxic effects and death from subsequent stem-cell transplant – “a consequence that is avoided with targeted therapy.”
 

Unanswered questions

“Will the excellent outcomes be preserved with longer follow-up? The answer is probably yes, given that the majority of relapses in ALL occur within the first 1.5 to 2.0 years after the initiation of treatment,” Dr. Hoelzer wrote.

He said other outstanding questions include whether long-term outcomes will differ between patients who undergo transplant and those who do not; whether ABL1 mutations emerge; whether minimal residual disease recurs with longer follow-up; and whether this treatment approach can be used for patients with other subtypes of ALL, such as Ph-negative, B-lineage ALL, or even T-cell ALL.

“If these promising trial results hold, chemotherapy-free induction without the immediate and long-term toxic effects of intensive chemotherapy regimens could also be used in adolescents and, finally, in children. These questions will need to be addressed with longer follow-up and large, prospective trials,” Dr. Hoelzer concluded.

The study was supported by grants from the Italian Association for Cancer Research and Sapienza University of Rome.

A version of this article originally appeared on Medscape.com

Immunotherapy is a rising star among emerging therapies for acute lymphoblastic leukemia (ALL), according to Patrick A. Brown, MD.

“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”

Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
 

Why immunotherapy?

“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.

These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.

“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
 

Inotuzumab, blinatumomab, and CAR T cells

Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.

“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”

Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.

CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.

Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.

Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.

“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.

CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.

“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”

Toxicities and limitations

Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.

“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.

A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.

Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.

Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.

Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
 

NCCN Treatment Guidelines

Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.

Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.

Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
 

Treatment decision making

Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.

“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.

“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”

An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”

In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.

“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.

Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.

[email protected]

Immunotherapy is a rising star among emerging therapies for acute lymphoblastic leukemia (ALL), according to Patrick A. Brown, MD.

“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”

Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
 

Why immunotherapy?

“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.

These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.

“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
 

Inotuzumab, blinatumomab, and CAR T cells

Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.

“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”

Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.

CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.

Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.

Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.

“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.

CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.

“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”

Toxicities and limitations

Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.

“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.

A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.

Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.

Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.

Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
 

NCCN Treatment Guidelines

Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.

Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.

Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
 

Treatment decision making

Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.

“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.

“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”

An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”

In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.

“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.

Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.

[email protected]

Immunotherapy is a rising star among emerging therapies for acute lymphoblastic leukemia (ALL), according to Patrick A. Brown, MD.

“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”

Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
 

Why immunotherapy?

“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.

These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.

“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
 

Inotuzumab, blinatumomab, and CAR T cells

Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.

“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”

Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.

CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.

Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.

Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.

“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.

CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.

“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”

Toxicities and limitations

Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.

“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.

A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.

Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.

Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.

Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
 

NCCN Treatment Guidelines

Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.

Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.

Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
 

Treatment decision making

Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.

“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.

“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”

An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”

In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.

“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.

Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.

[email protected]

Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.

Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.

Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.

Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.

For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.

For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.

These issues make it attractive to consider whether telehealth could be used for palliative care services.
 

Scarcity of palliative care specialists

In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.

In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.

For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.

Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
 

Special considerations regarding telehealth for palliative care

As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.

Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.

Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.

Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
 

REACH PC study demonstrates feasibility of telehealth model

Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.

The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.

Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.

Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).

Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.

Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).

When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.

When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.

The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
 

‘Webside’ manner

Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.

For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
 

Is telehealth the future of palliative care?

I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.

To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.

In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.

For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.

Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”

The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.

Dr. Temel disclosed institutional research funding from Pfizer.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.

Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.

Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.

Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.

For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.

For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.

These issues make it attractive to consider whether telehealth could be used for palliative care services.
 

Scarcity of palliative care specialists

In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.

In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.

For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.

Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
 

Special considerations regarding telehealth for palliative care

As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.

Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.

Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.

Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
 

REACH PC study demonstrates feasibility of telehealth model

Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.

The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.

Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.

Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).

Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.

Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).

When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.

When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.

The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
 

‘Webside’ manner

Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.

For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
 

Is telehealth the future of palliative care?

I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.

To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.

In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.

For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.

Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”

The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.

Dr. Temel disclosed institutional research funding from Pfizer.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.

Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.

Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.

Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.

For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.

For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.

These issues make it attractive to consider whether telehealth could be used for palliative care services.
 

Scarcity of palliative care specialists

In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.

In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.

For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.

Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
 

Special considerations regarding telehealth for palliative care

As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.

Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.

Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.

Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
 

REACH PC study demonstrates feasibility of telehealth model

Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.

The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.

Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.

Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).

Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.

Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).

When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.

When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.

The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
 

‘Webside’ manner

Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.

For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
 

Is telehealth the future of palliative care?

I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.

To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.

In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.

For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.

Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”

The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.

Dr. Temel disclosed institutional research funding from Pfizer.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.