User login
Repurposed drug could revolutionize stem cell transplantation
When the Food and Drug Administration approved abatacept in December 2021 as prophylaxis for acute graft-versus-host disease (aGVHD) in adults and children 2 years and older who are undergoing hematopoietic stem cell transplantation (HSCT), the announcement was notable for couple of key reasons.
Abatacept was approved based on results from the ABA2 trial, which evaluated 142 adults and children with hematologic malignancies who received a four-dose regimen of abatacept in addition to standard of care – a calcineurin inhibitor (CNI) plus methotrexate (MTX) – prior to undergoing an 8/8 HLA-matched, unrelated donor (URD) HSCT, or standard of care alone.
Another arm of the trial examined 43 recipients of a 7/8 HLA-mismatched URD HSCT who received abatacept plus standard of care, compared with a prespecified registry cohort group provided by the Center for International Blood and Marrow Transplant Research, who received CNI and MTX.
Results published in the Journal of Clinical Oncology showed the proportion of patients in the 8/8 group with severe aGVHD in the abatacept group 100 days after HSCT was not significantly lower, compared with the standard of care group (6.8% vs. 14.8%; P = .13), but there was a significant improvement in severe aGVHD–free survival (SGFS) 180 days after HSCT in the abatacept group, compared with the group that received standard of care (93.2% vs. 80%; P = .05).
Among patients in the 7/8 group, there was a significant difference in the proportion of patients with severe aGVHD favoring the abatacept group (2.3% vs. 30.2%; P < .001), and significantly improved SGFS, compared with the CIBMTR registry cohort (97.7% vs. 58.7%; P < .001)
A post hoc analysis of ABA2 published as a research letter in Blood Advances assessed abatacept using real-world data from CIBMTR. Researchers compared the 8/8 group that received standard of care with the 7/8 group that received abatacept plus standard of care and found no significant differences between relapse-free survival and overall survival for patients in the 8/8 group (adjusted hazard ratio, 0.60; 95% confidence interval, 0.28-1.28; P = .19) and 7/8 group (aHR, 0.77; 95% CI, 0.34-1.71; P = .51).
The results suggest “abatacept may eliminate that risk of a mismatched transplant in the setting of that analysis and that small cohort that was assessed there, which is good news for patients that may not have a fully matched donor on the registry,” said Stephen Spellman, vice president at Be The Match Research (operated by the National Marrow Donor Program), and senior scientific director of CIBMTR. The findings from ABA2 “were even more impressive than necessarily expected, especially in the 7/8 arm. This is a truly substantial reduction in acute GVHD risk in that patient population,” he said in an interview.
Could abatacept fuel greater use of mismatched, unrelated donors?
One downside of using an HLA-mismatched donor is the potential risk of developing aGVHD, Doris M. Ponce, MD, a hematologic oncologist with Memorial Sloan Kettering Cancer Center in New York, who was not involved with the research, said in an interview.
Potential risk factors for aGVHD include “having a female multiparous donor, HLA-mismatched donor, unrelated donor, donor and recipient age (>40 years), [peripheral blood stem cell] stem cell graft, recipient [cytomegalovirus] serostatus (recipient/donor), myeloablative conditioning, [total body irradiation]–based conditioning, [and] gut microbiome dysbiosis,” Dr. Ponce explained.
Abatacept’s approval may have particular relevance for people of color. “It’s been understood for a long time that the likelihood of finding an 8/8 well-matched, volunteer unrelated donor varies by race or ethnicity,” Steven Devine, MD, a board-certified oncologist who is chief medical officer of Be The Match and associate scientific director at CIBMTR, said in an interview.
Mr. Spellman noted that, of the more than 35 million donors on worldwide registries accessible through the National Marrow Donor Program’s Be The Match Registry, “the match rates differ quite substantially by race and ethnicity.” Approximately 29% of African Americans find a full match on the registry, compared with 81% of Whites, 49% of Hispanics, and 47% Asian/Pacific Islanders.
“Being able to utilize a 7/8 match in a safe, effective manner using abatacept, which abatacept has been approved for, does increase those match rates quite substantially,” he explained. Among African Americans, this means the match rate increases to 84%, among Hispanics and Asian/Pacific Islanders to approximately 90%, and among Whites to about 98%.
That kind of improvement in the match rate is “the equivalent of adding more than more than 10 million ethnically diverse donors to the registry in 1 day,” Dr. Devine said. “The availability of abatacept could really level the playing field for patients in need of a lifesaving transplant.”
Further study of abatacept
With abatacept, “I think the results are really encouraging, and I think that further studies [are needed] to better define how the drug would work and whether it can later prevent chronic graft versus host disease,” Dr. Devine said. He said the ABA3 trial has been designed around this question, with the hypothesis that extending abatacept to an eight-dose regimen may help with chronic GVHD.
Although the FDA’s approval of abatacept was recent, Mr. Spellman said, Be The Match has seen early indications that mismatched donors in the registry are being used, which may point to an increased utilization of abatacept. “Through October to December of 2021, there was a pretty substantial increase in the use of mismatched, unrelated donors in that time frame.”
Dr. Devine noted that he is seeing a lot of interest in using abatacept. “I think people are still learning how best to incorporate it into their standard of care right now.”
Meanwhile, Memorial Sloan Kettering Cancer Center is already planning to use abatacept, Dr. Ponce noted. “We have abatacept in our formulary for adult and children, and are planning on using it for patients receiving an unmodified graft from a [matched unrelated donor] or 1-allele [mismatched unrelated donor] using CNI and MTX-based GVHD prophylaxis.”
Dr. Devine and Mr. Spellman are employees of Be The Match and CIBMTR, which provided the registry control group for the ABA2 trial. Dr. Devine also reported that he has been a scientific advisory board member for Bristol-Myers Squibb. Dr. Ponce reports no relevant conflicts of interest.
When the Food and Drug Administration approved abatacept in December 2021 as prophylaxis for acute graft-versus-host disease (aGVHD) in adults and children 2 years and older who are undergoing hematopoietic stem cell transplantation (HSCT), the announcement was notable for couple of key reasons.
Abatacept was approved based on results from the ABA2 trial, which evaluated 142 adults and children with hematologic malignancies who received a four-dose regimen of abatacept in addition to standard of care – a calcineurin inhibitor (CNI) plus methotrexate (MTX) – prior to undergoing an 8/8 HLA-matched, unrelated donor (URD) HSCT, or standard of care alone.
Another arm of the trial examined 43 recipients of a 7/8 HLA-mismatched URD HSCT who received abatacept plus standard of care, compared with a prespecified registry cohort group provided by the Center for International Blood and Marrow Transplant Research, who received CNI and MTX.
Results published in the Journal of Clinical Oncology showed the proportion of patients in the 8/8 group with severe aGVHD in the abatacept group 100 days after HSCT was not significantly lower, compared with the standard of care group (6.8% vs. 14.8%; P = .13), but there was a significant improvement in severe aGVHD–free survival (SGFS) 180 days after HSCT in the abatacept group, compared with the group that received standard of care (93.2% vs. 80%; P = .05).
Among patients in the 7/8 group, there was a significant difference in the proportion of patients with severe aGVHD favoring the abatacept group (2.3% vs. 30.2%; P < .001), and significantly improved SGFS, compared with the CIBMTR registry cohort (97.7% vs. 58.7%; P < .001)
A post hoc analysis of ABA2 published as a research letter in Blood Advances assessed abatacept using real-world data from CIBMTR. Researchers compared the 8/8 group that received standard of care with the 7/8 group that received abatacept plus standard of care and found no significant differences between relapse-free survival and overall survival for patients in the 8/8 group (adjusted hazard ratio, 0.60; 95% confidence interval, 0.28-1.28; P = .19) and 7/8 group (aHR, 0.77; 95% CI, 0.34-1.71; P = .51).
The results suggest “abatacept may eliminate that risk of a mismatched transplant in the setting of that analysis and that small cohort that was assessed there, which is good news for patients that may not have a fully matched donor on the registry,” said Stephen Spellman, vice president at Be The Match Research (operated by the National Marrow Donor Program), and senior scientific director of CIBMTR. The findings from ABA2 “were even more impressive than necessarily expected, especially in the 7/8 arm. This is a truly substantial reduction in acute GVHD risk in that patient population,” he said in an interview.
Could abatacept fuel greater use of mismatched, unrelated donors?
One downside of using an HLA-mismatched donor is the potential risk of developing aGVHD, Doris M. Ponce, MD, a hematologic oncologist with Memorial Sloan Kettering Cancer Center in New York, who was not involved with the research, said in an interview.
Potential risk factors for aGVHD include “having a female multiparous donor, HLA-mismatched donor, unrelated donor, donor and recipient age (>40 years), [peripheral blood stem cell] stem cell graft, recipient [cytomegalovirus] serostatus (recipient/donor), myeloablative conditioning, [total body irradiation]–based conditioning, [and] gut microbiome dysbiosis,” Dr. Ponce explained.
Abatacept’s approval may have particular relevance for people of color. “It’s been understood for a long time that the likelihood of finding an 8/8 well-matched, volunteer unrelated donor varies by race or ethnicity,” Steven Devine, MD, a board-certified oncologist who is chief medical officer of Be The Match and associate scientific director at CIBMTR, said in an interview.
Mr. Spellman noted that, of the more than 35 million donors on worldwide registries accessible through the National Marrow Donor Program’s Be The Match Registry, “the match rates differ quite substantially by race and ethnicity.” Approximately 29% of African Americans find a full match on the registry, compared with 81% of Whites, 49% of Hispanics, and 47% Asian/Pacific Islanders.
“Being able to utilize a 7/8 match in a safe, effective manner using abatacept, which abatacept has been approved for, does increase those match rates quite substantially,” he explained. Among African Americans, this means the match rate increases to 84%, among Hispanics and Asian/Pacific Islanders to approximately 90%, and among Whites to about 98%.
That kind of improvement in the match rate is “the equivalent of adding more than more than 10 million ethnically diverse donors to the registry in 1 day,” Dr. Devine said. “The availability of abatacept could really level the playing field for patients in need of a lifesaving transplant.”
Further study of abatacept
With abatacept, “I think the results are really encouraging, and I think that further studies [are needed] to better define how the drug would work and whether it can later prevent chronic graft versus host disease,” Dr. Devine said. He said the ABA3 trial has been designed around this question, with the hypothesis that extending abatacept to an eight-dose regimen may help with chronic GVHD.
Although the FDA’s approval of abatacept was recent, Mr. Spellman said, Be The Match has seen early indications that mismatched donors in the registry are being used, which may point to an increased utilization of abatacept. “Through October to December of 2021, there was a pretty substantial increase in the use of mismatched, unrelated donors in that time frame.”
Dr. Devine noted that he is seeing a lot of interest in using abatacept. “I think people are still learning how best to incorporate it into their standard of care right now.”
Meanwhile, Memorial Sloan Kettering Cancer Center is already planning to use abatacept, Dr. Ponce noted. “We have abatacept in our formulary for adult and children, and are planning on using it for patients receiving an unmodified graft from a [matched unrelated donor] or 1-allele [mismatched unrelated donor] using CNI and MTX-based GVHD prophylaxis.”
Dr. Devine and Mr. Spellman are employees of Be The Match and CIBMTR, which provided the registry control group for the ABA2 trial. Dr. Devine also reported that he has been a scientific advisory board member for Bristol-Myers Squibb. Dr. Ponce reports no relevant conflicts of interest.
When the Food and Drug Administration approved abatacept in December 2021 as prophylaxis for acute graft-versus-host disease (aGVHD) in adults and children 2 years and older who are undergoing hematopoietic stem cell transplantation (HSCT), the announcement was notable for couple of key reasons.
Abatacept was approved based on results from the ABA2 trial, which evaluated 142 adults and children with hematologic malignancies who received a four-dose regimen of abatacept in addition to standard of care – a calcineurin inhibitor (CNI) plus methotrexate (MTX) – prior to undergoing an 8/8 HLA-matched, unrelated donor (URD) HSCT, or standard of care alone.
Another arm of the trial examined 43 recipients of a 7/8 HLA-mismatched URD HSCT who received abatacept plus standard of care, compared with a prespecified registry cohort group provided by the Center for International Blood and Marrow Transplant Research, who received CNI and MTX.
Results published in the Journal of Clinical Oncology showed the proportion of patients in the 8/8 group with severe aGVHD in the abatacept group 100 days after HSCT was not significantly lower, compared with the standard of care group (6.8% vs. 14.8%; P = .13), but there was a significant improvement in severe aGVHD–free survival (SGFS) 180 days after HSCT in the abatacept group, compared with the group that received standard of care (93.2% vs. 80%; P = .05).
Among patients in the 7/8 group, there was a significant difference in the proportion of patients with severe aGVHD favoring the abatacept group (2.3% vs. 30.2%; P < .001), and significantly improved SGFS, compared with the CIBMTR registry cohort (97.7% vs. 58.7%; P < .001)
A post hoc analysis of ABA2 published as a research letter in Blood Advances assessed abatacept using real-world data from CIBMTR. Researchers compared the 8/8 group that received standard of care with the 7/8 group that received abatacept plus standard of care and found no significant differences between relapse-free survival and overall survival for patients in the 8/8 group (adjusted hazard ratio, 0.60; 95% confidence interval, 0.28-1.28; P = .19) and 7/8 group (aHR, 0.77; 95% CI, 0.34-1.71; P = .51).
The results suggest “abatacept may eliminate that risk of a mismatched transplant in the setting of that analysis and that small cohort that was assessed there, which is good news for patients that may not have a fully matched donor on the registry,” said Stephen Spellman, vice president at Be The Match Research (operated by the National Marrow Donor Program), and senior scientific director of CIBMTR. The findings from ABA2 “were even more impressive than necessarily expected, especially in the 7/8 arm. This is a truly substantial reduction in acute GVHD risk in that patient population,” he said in an interview.
Could abatacept fuel greater use of mismatched, unrelated donors?
One downside of using an HLA-mismatched donor is the potential risk of developing aGVHD, Doris M. Ponce, MD, a hematologic oncologist with Memorial Sloan Kettering Cancer Center in New York, who was not involved with the research, said in an interview.
Potential risk factors for aGVHD include “having a female multiparous donor, HLA-mismatched donor, unrelated donor, donor and recipient age (>40 years), [peripheral blood stem cell] stem cell graft, recipient [cytomegalovirus] serostatus (recipient/donor), myeloablative conditioning, [total body irradiation]–based conditioning, [and] gut microbiome dysbiosis,” Dr. Ponce explained.
Abatacept’s approval may have particular relevance for people of color. “It’s been understood for a long time that the likelihood of finding an 8/8 well-matched, volunteer unrelated donor varies by race or ethnicity,” Steven Devine, MD, a board-certified oncologist who is chief medical officer of Be The Match and associate scientific director at CIBMTR, said in an interview.
Mr. Spellman noted that, of the more than 35 million donors on worldwide registries accessible through the National Marrow Donor Program’s Be The Match Registry, “the match rates differ quite substantially by race and ethnicity.” Approximately 29% of African Americans find a full match on the registry, compared with 81% of Whites, 49% of Hispanics, and 47% Asian/Pacific Islanders.
“Being able to utilize a 7/8 match in a safe, effective manner using abatacept, which abatacept has been approved for, does increase those match rates quite substantially,” he explained. Among African Americans, this means the match rate increases to 84%, among Hispanics and Asian/Pacific Islanders to approximately 90%, and among Whites to about 98%.
That kind of improvement in the match rate is “the equivalent of adding more than more than 10 million ethnically diverse donors to the registry in 1 day,” Dr. Devine said. “The availability of abatacept could really level the playing field for patients in need of a lifesaving transplant.”
Further study of abatacept
With abatacept, “I think the results are really encouraging, and I think that further studies [are needed] to better define how the drug would work and whether it can later prevent chronic graft versus host disease,” Dr. Devine said. He said the ABA3 trial has been designed around this question, with the hypothesis that extending abatacept to an eight-dose regimen may help with chronic GVHD.
Although the FDA’s approval of abatacept was recent, Mr. Spellman said, Be The Match has seen early indications that mismatched donors in the registry are being used, which may point to an increased utilization of abatacept. “Through October to December of 2021, there was a pretty substantial increase in the use of mismatched, unrelated donors in that time frame.”
Dr. Devine noted that he is seeing a lot of interest in using abatacept. “I think people are still learning how best to incorporate it into their standard of care right now.”
Meanwhile, Memorial Sloan Kettering Cancer Center is already planning to use abatacept, Dr. Ponce noted. “We have abatacept in our formulary for adult and children, and are planning on using it for patients receiving an unmodified graft from a [matched unrelated donor] or 1-allele [mismatched unrelated donor] using CNI and MTX-based GVHD prophylaxis.”
Dr. Devine and Mr. Spellman are employees of Be The Match and CIBMTR, which provided the registry control group for the ABA2 trial. Dr. Devine also reported that he has been a scientific advisory board member for Bristol-Myers Squibb. Dr. Ponce reports no relevant conflicts of interest.
Hodgkin-directed therapy may benefit patients with rare CLL subtype
Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.
Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.
Given the rarity of CLL-HRS, data on patient management are limited, they noted.
In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.
The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.
The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).
CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).
Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.
“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.
The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.
However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.
“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.
In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”
“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”
“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.
The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
This article was updated 3/11/22.
Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.
Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.
Given the rarity of CLL-HRS, data on patient management are limited, they noted.
In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.
The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.
The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).
CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).
Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.
“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.
The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.
However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.
“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.
In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”
“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”
“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.
The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
This article was updated 3/11/22.
Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.
Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.
Given the rarity of CLL-HRS, data on patient management are limited, they noted.
In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.
The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.
The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).
CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).
Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.
“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.
The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.
However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.
“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.
In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”
“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”
“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.
The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
This article was updated 3/11/22.
FROM BLOOD CANCER JOURNAL
DKMS: Small nonprofit to world’s largest stem cell donor registry
When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.
“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.
In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.
“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.
Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).
In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”
From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.
Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
World’s largest registry
“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.
“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,
Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.
Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
Global partners
DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.
“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.
The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
Pandemic affects donations
But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.
Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.
“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.
However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.
“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
Workforce and clinical problems
Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.
“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.
“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.
Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.
“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.
In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.
“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.
To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.
The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
‘Every patient saved’
The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.
DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.
In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.
The last word goes to Mechtild Harf’s daughter Katharina.
“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”
“I have to believe that this dream will come true because otherwise, why dream, right?” she said.
Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.
When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.
“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.
In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.
“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.
Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).
In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”
From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.
Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
World’s largest registry
“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.
“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,
Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.
Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
Global partners
DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.
“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.
The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
Pandemic affects donations
But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.
Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.
“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.
However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.
“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
Workforce and clinical problems
Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.
“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.
“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.
Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.
“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.
In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.
“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.
To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.
The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
‘Every patient saved’
The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.
DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.
In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.
The last word goes to Mechtild Harf’s daughter Katharina.
“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”
“I have to believe that this dream will come true because otherwise, why dream, right?” she said.
Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.
When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.
“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.
In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.
“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.
Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).
In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”
From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.
Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
World’s largest registry
“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.
“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,
Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.
Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
Global partners
DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.
“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.
The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
Pandemic affects donations
But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.
Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.
“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.
However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.
“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
Workforce and clinical problems
Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.
“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.
“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.
Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.
“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.
In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.
“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.
To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.
The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
‘Every patient saved’
The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.
DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.
In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.
The last word goes to Mechtild Harf’s daughter Katharina.
“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”
“I have to believe that this dream will come true because otherwise, why dream, right?” she said.
Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.
Frontline brentuximab vedotin shows promise in high-risk pediatric Hodgkin lymphoma
A frontline treatment regimen including brentuximab vedotin (Bv) was well tolerated, was highly effective, and significantly reduced radiation exposure in pediatric patients with high-risk Hodgkin lymphoma, according to the results of an open-label, phase 2 trial.
Of 77 patients enrolled in the investigator-initiated, single-arm, multicenter trial, 27 (35%) achieved complete remission (CR) without radiation at the early response assessment (ERA) after two cycles of therapy, reported Monika L. Metzger, MD, of St. Jude Children’s Research Hospital, Memphis, Tenn. and colleagues. The report was published online in the Journal of Clinical Oncology.
The addition of Bv also resulted in superior event-free survival (97.4%) and overall survival (98.7%) at median follow-up of 3.4 years, compared with previously published pediatric trials, such as the HOD99 trial (EFS and OS of 80.8% and 96.5%, respectively), the authors noted.
Bv chemotherapy
Bv, a targeted anti-CD30 antibody-drug conjugate, received expanded Food and Drug Administration approval in March 2018 for frontline use in combination with chemotherapy in adults with stage III or IV classical Hodgkin lymphoma (HL). The current study is the first to include Bv as part of a chemotherapy regimen in the frontline setting for pediatric classical HL, the authors noted, adding that their primary aim was to reduce prescribed radiation thereby limiting late toxicities associated with radiation in this population.
Patients enrolled were children and adolescents aged 18 years and under with stage IIB, IIIB, or IV classical HL. Bv was used in place of vincristine in the standard OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) frontline regimen for pediatric HL.
The Bv-based chemotherapy regimen was well tolerated and mostly limited to low-grade nausea, vomiting, and constipation, and the most common adverse events were hematologic events occurring mainly during the first two cycles of chemotherapy.
“Notably, we observed a very low incidence of neuropathy (4%) by both clinician and patient report, and no participants required Bv dose reduction or discontinuation,” they wrote, explaining that neuropathy is more common with vincristine.
Radiation exposure
Residual node radiotherapy (RNRT) was delivered at a prescribed dose of 25.5 Gy in 17 fractions of 1.5 Gy, 2-4 weeks after completion of chemotherapy only to nodal sites that did not achieve a CR at the early response assessment (ERA) after two cycles of therapy.
“Patients treated with RNRT had significantly lower integral radiation dose compared with patients treated on HOD99 with [involved-field radiation therapy] (78.1 J vs. 249.6 J),” the authors wrote. “Doses to specific organs were also compared ... [t]he mean heart dose was reduced to 5.29 Gy from 16.9 Gy, and the mean thyroid dose was reduced to 4.46 Gy from 25.9 Gy.”
Women also had significantly less breast radiation exposure (mean of 3.21 Gy vs. 6.85 Gy in HOD99).
One irradiated patient experienced disease progression at the end of therapy, but remained disease free more than 6 years following salvage therapy, and one unexpected death occurred, the authors said.
“We have already reduced the use of radiation for low-risk Hodgkin lymphoma patients. In this study we’ve shown that it is also possible to either omit or reduce the extent of radiation for high-risk patients, using highly focal methods such as proton beam radiation or intensity modulated radiation,” co–senior author Matthew Krasin, MD, of St. Jude’s department of radiation oncology, stated in a press release.
Next steps
Co–senior author Melissa Hudson, MD, the St. Jude cancer survivorship division director, added that “[b]eing able to offer Hodgkin lymphoma patients a targeted therapy in the frontline setting is an exciting development.
“The favorable safety and toxicity profile of Bv in combination with chemotherapy for high-risk pediatric patients supports its prospective evaluation in a randomized trial,” the authors concluded, noting that “[l]onger follow-up is required to establish if this approach reduces risk of late-occurring toxicities such as second malignant neoplasms in this cohort of minimally irradiated patients.”
The study was sponsored by Seattle Genetics. The research at St. Jude was funded in part by grants from the National Cancer Institute and ALSAC (American Lebanese Syrian Associated Charities), St. Jude’s fundraising and awareness organization. Dr. Metzger reported research funding from Seattle Genetics. Dr. Krasin reported a consulting or advisory role for Debiopharm Group. Dr. Hudson reported a consulting or advisory role for Oncology Research Information Exchange Network, Princess Máxima Center.
A frontline treatment regimen including brentuximab vedotin (Bv) was well tolerated, was highly effective, and significantly reduced radiation exposure in pediatric patients with high-risk Hodgkin lymphoma, according to the results of an open-label, phase 2 trial.
Of 77 patients enrolled in the investigator-initiated, single-arm, multicenter trial, 27 (35%) achieved complete remission (CR) without radiation at the early response assessment (ERA) after two cycles of therapy, reported Monika L. Metzger, MD, of St. Jude Children’s Research Hospital, Memphis, Tenn. and colleagues. The report was published online in the Journal of Clinical Oncology.
The addition of Bv also resulted in superior event-free survival (97.4%) and overall survival (98.7%) at median follow-up of 3.4 years, compared with previously published pediatric trials, such as the HOD99 trial (EFS and OS of 80.8% and 96.5%, respectively), the authors noted.
Bv chemotherapy
Bv, a targeted anti-CD30 antibody-drug conjugate, received expanded Food and Drug Administration approval in March 2018 for frontline use in combination with chemotherapy in adults with stage III or IV classical Hodgkin lymphoma (HL). The current study is the first to include Bv as part of a chemotherapy regimen in the frontline setting for pediatric classical HL, the authors noted, adding that their primary aim was to reduce prescribed radiation thereby limiting late toxicities associated with radiation in this population.
Patients enrolled were children and adolescents aged 18 years and under with stage IIB, IIIB, or IV classical HL. Bv was used in place of vincristine in the standard OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) frontline regimen for pediatric HL.
The Bv-based chemotherapy regimen was well tolerated and mostly limited to low-grade nausea, vomiting, and constipation, and the most common adverse events were hematologic events occurring mainly during the first two cycles of chemotherapy.
“Notably, we observed a very low incidence of neuropathy (4%) by both clinician and patient report, and no participants required Bv dose reduction or discontinuation,” they wrote, explaining that neuropathy is more common with vincristine.
Radiation exposure
Residual node radiotherapy (RNRT) was delivered at a prescribed dose of 25.5 Gy in 17 fractions of 1.5 Gy, 2-4 weeks after completion of chemotherapy only to nodal sites that did not achieve a CR at the early response assessment (ERA) after two cycles of therapy.
“Patients treated with RNRT had significantly lower integral radiation dose compared with patients treated on HOD99 with [involved-field radiation therapy] (78.1 J vs. 249.6 J),” the authors wrote. “Doses to specific organs were also compared ... [t]he mean heart dose was reduced to 5.29 Gy from 16.9 Gy, and the mean thyroid dose was reduced to 4.46 Gy from 25.9 Gy.”
Women also had significantly less breast radiation exposure (mean of 3.21 Gy vs. 6.85 Gy in HOD99).
One irradiated patient experienced disease progression at the end of therapy, but remained disease free more than 6 years following salvage therapy, and one unexpected death occurred, the authors said.
“We have already reduced the use of radiation for low-risk Hodgkin lymphoma patients. In this study we’ve shown that it is also possible to either omit or reduce the extent of radiation for high-risk patients, using highly focal methods such as proton beam radiation or intensity modulated radiation,” co–senior author Matthew Krasin, MD, of St. Jude’s department of radiation oncology, stated in a press release.
Next steps
Co–senior author Melissa Hudson, MD, the St. Jude cancer survivorship division director, added that “[b]eing able to offer Hodgkin lymphoma patients a targeted therapy in the frontline setting is an exciting development.
“The favorable safety and toxicity profile of Bv in combination with chemotherapy for high-risk pediatric patients supports its prospective evaluation in a randomized trial,” the authors concluded, noting that “[l]onger follow-up is required to establish if this approach reduces risk of late-occurring toxicities such as second malignant neoplasms in this cohort of minimally irradiated patients.”
The study was sponsored by Seattle Genetics. The research at St. Jude was funded in part by grants from the National Cancer Institute and ALSAC (American Lebanese Syrian Associated Charities), St. Jude’s fundraising and awareness organization. Dr. Metzger reported research funding from Seattle Genetics. Dr. Krasin reported a consulting or advisory role for Debiopharm Group. Dr. Hudson reported a consulting or advisory role for Oncology Research Information Exchange Network, Princess Máxima Center.
A frontline treatment regimen including brentuximab vedotin (Bv) was well tolerated, was highly effective, and significantly reduced radiation exposure in pediatric patients with high-risk Hodgkin lymphoma, according to the results of an open-label, phase 2 trial.
Of 77 patients enrolled in the investigator-initiated, single-arm, multicenter trial, 27 (35%) achieved complete remission (CR) without radiation at the early response assessment (ERA) after two cycles of therapy, reported Monika L. Metzger, MD, of St. Jude Children’s Research Hospital, Memphis, Tenn. and colleagues. The report was published online in the Journal of Clinical Oncology.
The addition of Bv also resulted in superior event-free survival (97.4%) and overall survival (98.7%) at median follow-up of 3.4 years, compared with previously published pediatric trials, such as the HOD99 trial (EFS and OS of 80.8% and 96.5%, respectively), the authors noted.
Bv chemotherapy
Bv, a targeted anti-CD30 antibody-drug conjugate, received expanded Food and Drug Administration approval in March 2018 for frontline use in combination with chemotherapy in adults with stage III or IV classical Hodgkin lymphoma (HL). The current study is the first to include Bv as part of a chemotherapy regimen in the frontline setting for pediatric classical HL, the authors noted, adding that their primary aim was to reduce prescribed radiation thereby limiting late toxicities associated with radiation in this population.
Patients enrolled were children and adolescents aged 18 years and under with stage IIB, IIIB, or IV classical HL. Bv was used in place of vincristine in the standard OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) frontline regimen for pediatric HL.
The Bv-based chemotherapy regimen was well tolerated and mostly limited to low-grade nausea, vomiting, and constipation, and the most common adverse events were hematologic events occurring mainly during the first two cycles of chemotherapy.
“Notably, we observed a very low incidence of neuropathy (4%) by both clinician and patient report, and no participants required Bv dose reduction or discontinuation,” they wrote, explaining that neuropathy is more common with vincristine.
Radiation exposure
Residual node radiotherapy (RNRT) was delivered at a prescribed dose of 25.5 Gy in 17 fractions of 1.5 Gy, 2-4 weeks after completion of chemotherapy only to nodal sites that did not achieve a CR at the early response assessment (ERA) after two cycles of therapy.
“Patients treated with RNRT had significantly lower integral radiation dose compared with patients treated on HOD99 with [involved-field radiation therapy] (78.1 J vs. 249.6 J),” the authors wrote. “Doses to specific organs were also compared ... [t]he mean heart dose was reduced to 5.29 Gy from 16.9 Gy, and the mean thyroid dose was reduced to 4.46 Gy from 25.9 Gy.”
Women also had significantly less breast radiation exposure (mean of 3.21 Gy vs. 6.85 Gy in HOD99).
One irradiated patient experienced disease progression at the end of therapy, but remained disease free more than 6 years following salvage therapy, and one unexpected death occurred, the authors said.
“We have already reduced the use of radiation for low-risk Hodgkin lymphoma patients. In this study we’ve shown that it is also possible to either omit or reduce the extent of radiation for high-risk patients, using highly focal methods such as proton beam radiation or intensity modulated radiation,” co–senior author Matthew Krasin, MD, of St. Jude’s department of radiation oncology, stated in a press release.
Next steps
Co–senior author Melissa Hudson, MD, the St. Jude cancer survivorship division director, added that “[b]eing able to offer Hodgkin lymphoma patients a targeted therapy in the frontline setting is an exciting development.
“The favorable safety and toxicity profile of Bv in combination with chemotherapy for high-risk pediatric patients supports its prospective evaluation in a randomized trial,” the authors concluded, noting that “[l]onger follow-up is required to establish if this approach reduces risk of late-occurring toxicities such as second malignant neoplasms in this cohort of minimally irradiated patients.”
The study was sponsored by Seattle Genetics. The research at St. Jude was funded in part by grants from the National Cancer Institute and ALSAC (American Lebanese Syrian Associated Charities), St. Jude’s fundraising and awareness organization. Dr. Metzger reported research funding from Seattle Genetics. Dr. Krasin reported a consulting or advisory role for Debiopharm Group. Dr. Hudson reported a consulting or advisory role for Oncology Research Information Exchange Network, Princess Máxima Center.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Don’t delay: Cancer patients need both doses of COVID vaccine
The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.
Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.
The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).
This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.
The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).
The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.
Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.
“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.
“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.
The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.
These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.
“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”
Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.
Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.
“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”
Study details
Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.
There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”
To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.
The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.
The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.
All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.
The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.
The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).
T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.
Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.
Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.
The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.
Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.
The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).
This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.
The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).
The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.
Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.
“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.
“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.
The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.
These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.
“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”
Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.
Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.
“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”
Study details
Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.
There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”
To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.
The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.
The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.
All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.
The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.
The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).
T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.
Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.
Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.
The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.
Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.
The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).
This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.
The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).
The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.
Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.
“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.
“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.
The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.
These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.
“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”
Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.
Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.
“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”
Study details
Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.
There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”
To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.
The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.
The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.
All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.
The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.
The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).
T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.
Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.
Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.
The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Childhood Hodgkin survivors have neurocognitive impairment
More than 2 decades on, adult survivors of childhood Hodgkin lymphoma report significantly more neurocognitive impairment than their siblings, but the differences may be related to risk factors in adulthood rather than to treatment in childhood, investigators say.
Among adults with a history of childhood Hodgkin lymphoma and their siblings as controls, the survivors reported significantly worse functioning than their brothers or sisters in four domains of neurocognitive functioning.
In multivariate analysis, however, while sex, race, activity level and smoking status were all significant predictors for worse neurocognitive impairment, there were no significant associations between chemotherapy drugs or chest radiation and neurocognitive impairment, said Annalynn M. Williams, PhD, from St. Jude Children’s Research Hospital in Memphis.
“Hodgkin lymphoma is the most common cancer diagnosed in adolescents, and for many years we’ve had high cure rates, resulting in a growing population of survivors who are now, unfortunately, at an increased risk for cardiovascular, respiratory, endocrine and neurologic late morbidity. The neurocognitive morbidity in this population, however, is unknown,” she said in oral abstract presented at the annual meeting of the American Society of Hematology.
Survivors and sibs
To better characterize the potential late neurocognitive effects of intensive Hodgkin lymphoma therapy in childhood, Dr. Williams and colleagues polled survivors of childhood Hodgkin lymphoma and randomly selected sibling controls who were participants in the Childhood Cancer Survivor Study (CCSS).
Participants were asked to complete questionnaires regarding four domains of neurocognitive impairment: task efficiency, emotional regulation, organization, and memory. The investigators defined impairment in each domain as a score lower than that of the 90th percentile of community controls from the St. Jude Lifetime Cohort.
A total of 1,564 survivors and 725 controls completed the questionnaires and were included in the study.
The median age at follow-up was slightly higher among survivors, at 37 versus 32 years. The median age at diagnosis was 14, and the median time since diagnosis was 23 years.
In all, 10.8% of survivors reported impaired task efficiency, compared with 7.7% of controls. Problems with emotional regulation were reported by 16.6% of survivors versus 11.5% of siblings, and difficulties with organization and memory were reported by 12.1% versus10.3%, and 8.1% versus 5.7%, respectively.
In a model adjusted for age, sex, and race, the relative risks for neurocognitive impairment among survivors versus siblings, were as follows: task efficiency (RR,1.37); emotional regulation (RR, 1.56); organization (RR, 1.32); memory (RR, 1.72) (all significant by confidence interval).
In a model adjusted for sex, race, smoking status, exercise, age, time since diagnosis, and treatment exposures, risk factors for neurocognitive impairment among survivors included female versus male sex (significant for emotional regulation and memory deficits); non-White versus White (significant for task efficiency); former smoker versus never (significant for all domains except organization); current smoker versus never (significant for task efficiency and emotional regulation); and meeting Centers for Disease Control and Prevention exercise criteria versus not (negatively significant for task efficiency and organization); (P < .05 for all above comparisons).
However, in a model adjusted for relapse, second malignancy, treatment exposures, age, sex, race, time since diagnosis, smoking status and physical activity, only relapse or second malignancy – surrogates for additional treatment exposures – were significantly associated with neurocognitive impairment, and then only in the domain of task efficiency.
Chronic conditions significantly associated with risk for impairment included cardiovascular disease (significant across all domains), respiratory comorbidities (significant for task efficiency), endocrine disorders (significant for task efficiency), and neurologic disorders (significant in all domains except organization).
“While these analyses give us a sense of the presence of neurocognitive impairment in a large sample of Hodgkin lymphoma survivors from across the U.S., these analyses are limited by the self-reported nature of the data,” Dr. Williams acknowledged.
“Because survivors self-report impairments, these likely represent overt, symptomatic neurocognitive impairments. Many more survivors may experience more subtle neurocognitive impairments, and additional research with objective measures of both chronic health conditions and neurocognitive functioning are warranted,” she added.
Smoking gun?
In the question-and-answer session following the presentation, session comoderator Pallawi Torka, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., who was not involved in the research, commented that the finding regarding a link between current and former smoking as risk factors for neurocognitive impairment was “intriguing.”
“Do you think that smoking is a cause or an effect of having that impairment in childhood survivors of Hodgkin lymphoma?” she asked.
“That’s a great question, and actually one we have spent a great deal of time discussing, and we’re still trying to tease that apart. We’re still not really sure where that association is coming from,” Dr. Williams replied.
She noted that, in a different sample of CCSS participants from whom biospecimens were collected, the investigators plan to see whether smoking drives inflammation and oxidative stress mechanisms that may be contributing to neurocognitive impairment, or whether smoking is a coping mechanism related to anxiety and depression, which have also been seen in survivors.
Kara Kelly, MD, a pediatric oncologist at Roswell Park, commented that some survivors report symptoms of cognitive dysfunction shortly after treatment, and asked whether there might be a relationship to Hodgkin-specific factors such as B symptoms, in which cytokine-mediated inflammation may play a role.
Dr. Williams said that, “unfortunately, in CCSS these survivors had to be at least 5 years from diagnosis, but in many cases were recruited years after their diagnosis and treatment, so we don’t have data on B symptoms.”
The CCSS is funded by the National Cancer Institute. Dr. Williams, Dr. Palawi, and Dr. Kelly all reported no relevant conflicts of interest to disclose.
SOURCE: Williams AM et al. ASH 2020, Abstract 370.
More than 2 decades on, adult survivors of childhood Hodgkin lymphoma report significantly more neurocognitive impairment than their siblings, but the differences may be related to risk factors in adulthood rather than to treatment in childhood, investigators say.
Among adults with a history of childhood Hodgkin lymphoma and their siblings as controls, the survivors reported significantly worse functioning than their brothers or sisters in four domains of neurocognitive functioning.
In multivariate analysis, however, while sex, race, activity level and smoking status were all significant predictors for worse neurocognitive impairment, there were no significant associations between chemotherapy drugs or chest radiation and neurocognitive impairment, said Annalynn M. Williams, PhD, from St. Jude Children’s Research Hospital in Memphis.
“Hodgkin lymphoma is the most common cancer diagnosed in adolescents, and for many years we’ve had high cure rates, resulting in a growing population of survivors who are now, unfortunately, at an increased risk for cardiovascular, respiratory, endocrine and neurologic late morbidity. The neurocognitive morbidity in this population, however, is unknown,” she said in oral abstract presented at the annual meeting of the American Society of Hematology.
Survivors and sibs
To better characterize the potential late neurocognitive effects of intensive Hodgkin lymphoma therapy in childhood, Dr. Williams and colleagues polled survivors of childhood Hodgkin lymphoma and randomly selected sibling controls who were participants in the Childhood Cancer Survivor Study (CCSS).
Participants were asked to complete questionnaires regarding four domains of neurocognitive impairment: task efficiency, emotional regulation, organization, and memory. The investigators defined impairment in each domain as a score lower than that of the 90th percentile of community controls from the St. Jude Lifetime Cohort.
A total of 1,564 survivors and 725 controls completed the questionnaires and were included in the study.
The median age at follow-up was slightly higher among survivors, at 37 versus 32 years. The median age at diagnosis was 14, and the median time since diagnosis was 23 years.
In all, 10.8% of survivors reported impaired task efficiency, compared with 7.7% of controls. Problems with emotional regulation were reported by 16.6% of survivors versus 11.5% of siblings, and difficulties with organization and memory were reported by 12.1% versus10.3%, and 8.1% versus 5.7%, respectively.
In a model adjusted for age, sex, and race, the relative risks for neurocognitive impairment among survivors versus siblings, were as follows: task efficiency (RR,1.37); emotional regulation (RR, 1.56); organization (RR, 1.32); memory (RR, 1.72) (all significant by confidence interval).
In a model adjusted for sex, race, smoking status, exercise, age, time since diagnosis, and treatment exposures, risk factors for neurocognitive impairment among survivors included female versus male sex (significant for emotional regulation and memory deficits); non-White versus White (significant for task efficiency); former smoker versus never (significant for all domains except organization); current smoker versus never (significant for task efficiency and emotional regulation); and meeting Centers for Disease Control and Prevention exercise criteria versus not (negatively significant for task efficiency and organization); (P < .05 for all above comparisons).
However, in a model adjusted for relapse, second malignancy, treatment exposures, age, sex, race, time since diagnosis, smoking status and physical activity, only relapse or second malignancy – surrogates for additional treatment exposures – were significantly associated with neurocognitive impairment, and then only in the domain of task efficiency.
Chronic conditions significantly associated with risk for impairment included cardiovascular disease (significant across all domains), respiratory comorbidities (significant for task efficiency), endocrine disorders (significant for task efficiency), and neurologic disorders (significant in all domains except organization).
“While these analyses give us a sense of the presence of neurocognitive impairment in a large sample of Hodgkin lymphoma survivors from across the U.S., these analyses are limited by the self-reported nature of the data,” Dr. Williams acknowledged.
“Because survivors self-report impairments, these likely represent overt, symptomatic neurocognitive impairments. Many more survivors may experience more subtle neurocognitive impairments, and additional research with objective measures of both chronic health conditions and neurocognitive functioning are warranted,” she added.
Smoking gun?
In the question-and-answer session following the presentation, session comoderator Pallawi Torka, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., who was not involved in the research, commented that the finding regarding a link between current and former smoking as risk factors for neurocognitive impairment was “intriguing.”
“Do you think that smoking is a cause or an effect of having that impairment in childhood survivors of Hodgkin lymphoma?” she asked.
“That’s a great question, and actually one we have spent a great deal of time discussing, and we’re still trying to tease that apart. We’re still not really sure where that association is coming from,” Dr. Williams replied.
She noted that, in a different sample of CCSS participants from whom biospecimens were collected, the investigators plan to see whether smoking drives inflammation and oxidative stress mechanisms that may be contributing to neurocognitive impairment, or whether smoking is a coping mechanism related to anxiety and depression, which have also been seen in survivors.
Kara Kelly, MD, a pediatric oncologist at Roswell Park, commented that some survivors report symptoms of cognitive dysfunction shortly after treatment, and asked whether there might be a relationship to Hodgkin-specific factors such as B symptoms, in which cytokine-mediated inflammation may play a role.
Dr. Williams said that, “unfortunately, in CCSS these survivors had to be at least 5 years from diagnosis, but in many cases were recruited years after their diagnosis and treatment, so we don’t have data on B symptoms.”
The CCSS is funded by the National Cancer Institute. Dr. Williams, Dr. Palawi, and Dr. Kelly all reported no relevant conflicts of interest to disclose.
SOURCE: Williams AM et al. ASH 2020, Abstract 370.
More than 2 decades on, adult survivors of childhood Hodgkin lymphoma report significantly more neurocognitive impairment than their siblings, but the differences may be related to risk factors in adulthood rather than to treatment in childhood, investigators say.
Among adults with a history of childhood Hodgkin lymphoma and their siblings as controls, the survivors reported significantly worse functioning than their brothers or sisters in four domains of neurocognitive functioning.
In multivariate analysis, however, while sex, race, activity level and smoking status were all significant predictors for worse neurocognitive impairment, there were no significant associations between chemotherapy drugs or chest radiation and neurocognitive impairment, said Annalynn M. Williams, PhD, from St. Jude Children’s Research Hospital in Memphis.
“Hodgkin lymphoma is the most common cancer diagnosed in adolescents, and for many years we’ve had high cure rates, resulting in a growing population of survivors who are now, unfortunately, at an increased risk for cardiovascular, respiratory, endocrine and neurologic late morbidity. The neurocognitive morbidity in this population, however, is unknown,” she said in oral abstract presented at the annual meeting of the American Society of Hematology.
Survivors and sibs
To better characterize the potential late neurocognitive effects of intensive Hodgkin lymphoma therapy in childhood, Dr. Williams and colleagues polled survivors of childhood Hodgkin lymphoma and randomly selected sibling controls who were participants in the Childhood Cancer Survivor Study (CCSS).
Participants were asked to complete questionnaires regarding four domains of neurocognitive impairment: task efficiency, emotional regulation, organization, and memory. The investigators defined impairment in each domain as a score lower than that of the 90th percentile of community controls from the St. Jude Lifetime Cohort.
A total of 1,564 survivors and 725 controls completed the questionnaires and were included in the study.
The median age at follow-up was slightly higher among survivors, at 37 versus 32 years. The median age at diagnosis was 14, and the median time since diagnosis was 23 years.
In all, 10.8% of survivors reported impaired task efficiency, compared with 7.7% of controls. Problems with emotional regulation were reported by 16.6% of survivors versus 11.5% of siblings, and difficulties with organization and memory were reported by 12.1% versus10.3%, and 8.1% versus 5.7%, respectively.
In a model adjusted for age, sex, and race, the relative risks for neurocognitive impairment among survivors versus siblings, were as follows: task efficiency (RR,1.37); emotional regulation (RR, 1.56); organization (RR, 1.32); memory (RR, 1.72) (all significant by confidence interval).
In a model adjusted for sex, race, smoking status, exercise, age, time since diagnosis, and treatment exposures, risk factors for neurocognitive impairment among survivors included female versus male sex (significant for emotional regulation and memory deficits); non-White versus White (significant for task efficiency); former smoker versus never (significant for all domains except organization); current smoker versus never (significant for task efficiency and emotional regulation); and meeting Centers for Disease Control and Prevention exercise criteria versus not (negatively significant for task efficiency and organization); (P < .05 for all above comparisons).
However, in a model adjusted for relapse, second malignancy, treatment exposures, age, sex, race, time since diagnosis, smoking status and physical activity, only relapse or second malignancy – surrogates for additional treatment exposures – were significantly associated with neurocognitive impairment, and then only in the domain of task efficiency.
Chronic conditions significantly associated with risk for impairment included cardiovascular disease (significant across all domains), respiratory comorbidities (significant for task efficiency), endocrine disorders (significant for task efficiency), and neurologic disorders (significant in all domains except organization).
“While these analyses give us a sense of the presence of neurocognitive impairment in a large sample of Hodgkin lymphoma survivors from across the U.S., these analyses are limited by the self-reported nature of the data,” Dr. Williams acknowledged.
“Because survivors self-report impairments, these likely represent overt, symptomatic neurocognitive impairments. Many more survivors may experience more subtle neurocognitive impairments, and additional research with objective measures of both chronic health conditions and neurocognitive functioning are warranted,” she added.
Smoking gun?
In the question-and-answer session following the presentation, session comoderator Pallawi Torka, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., who was not involved in the research, commented that the finding regarding a link between current and former smoking as risk factors for neurocognitive impairment was “intriguing.”
“Do you think that smoking is a cause or an effect of having that impairment in childhood survivors of Hodgkin lymphoma?” she asked.
“That’s a great question, and actually one we have spent a great deal of time discussing, and we’re still trying to tease that apart. We’re still not really sure where that association is coming from,” Dr. Williams replied.
She noted that, in a different sample of CCSS participants from whom biospecimens were collected, the investigators plan to see whether smoking drives inflammation and oxidative stress mechanisms that may be contributing to neurocognitive impairment, or whether smoking is a coping mechanism related to anxiety and depression, which have also been seen in survivors.
Kara Kelly, MD, a pediatric oncologist at Roswell Park, commented that some survivors report symptoms of cognitive dysfunction shortly after treatment, and asked whether there might be a relationship to Hodgkin-specific factors such as B symptoms, in which cytokine-mediated inflammation may play a role.
Dr. Williams said that, “unfortunately, in CCSS these survivors had to be at least 5 years from diagnosis, but in many cases were recruited years after their diagnosis and treatment, so we don’t have data on B symptoms.”
The CCSS is funded by the National Cancer Institute. Dr. Williams, Dr. Palawi, and Dr. Kelly all reported no relevant conflicts of interest to disclose.
SOURCE: Williams AM et al. ASH 2020, Abstract 370.
FROM ASH 2020
Efforts to close the ‘AYA gap’ in lymphoma
In the 1970s, cancer survival was poor for young children and older adults in the United States, as shown by data published in the Journal of the National Cancer Institute.
Great progress has been made since the 1970s, but improvements in outcome have been less impressive for cancer patients aged 15-39 years, as shown by research published in Cancer. 
Patients aged 15-39 years have been designated by the National Institutes of Health (NIH) as “adolescents and young adults (AYAs),” and the lag in survival benefit has been termed “the AYA gap.”
The AYA gap persists in lymphoma patients, and an expert panel recently outlined differences between lymphoma in AYAs and lymphoma in other age groups.
The experts spoke at a special session of the AACR Virtual Meeting: Advances in Malignant Lymphoma moderated by Somali M. Smith, MD, of the University of Chicago.
Factors that contribute to the AYA gap
About 89,000 AYAs are diagnosed with cancer each year in the United States, according to data from the National Cancer Institute (NCI). Lymphomas and thyroid cancer are the most common cancers among younger AYAs, aged 15-24 years.
In a report commissioned by the NIH in 2006, many factors contributing to the AYA gap were identified. Chief among them were:
- Limitations in access to care.
- Delayed diagnosis.
- Inconsistency in treatment and follow-up.
- Long-term toxicity (fertility, second malignancies, and cardiovascular disease).
These factors compromise health-related survival, even when cancer-specific survival is improved.
Panelist Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., noted that there are additional unique challenges for AYAs with cancer. These include:
- Pubertal changes.
- Developmental transition to independence.
- Societal impediments such as insurance coverage and disparities in access to specialized centers.
- Psychosocial factors such as health literacy and adherence to treatment and follow-up.
Focusing on lymphoma specifically, Dr. Kelly noted that lymphoma biology differs across the age spectrum and by race and ethnicity. Both tumor and host factors require further study, she said.
Clinical trial access for AYAs
Dr. Kelly emphasized that, unfortunately, clinical research participation is low among AYAs. A major impediment is that adult clinical trials historically required participants to be at least 18 years old.
In addition, there has not been a focused effort to educate AYAs about regulatory safeguards to ensure safety and the promise of enhanced benefit to them in NCI Cancer Trials Network (NCTN) trials. As a result, the refusal rate is high.
A multi-stakeholder workshop, convened in May 2016 by the American Society of Clinical Oncology and Friends of Cancer Research, outlined opportunities for expanding trial eligibility to include children younger than 18 years in first-in-human and other adult cancer clinical trials, enhancing their access to new agents, without compromising safety.
Recently, collaborative efforts between the adult and children’s NCTN research groups have included AYAs in studies addressing cancers that span the age spectrum, including lymphoma.
However, as Dr. Kelly noted, there are differences in AYA lymphoid malignancy types with a transition from more pediatric to more adult types.
Hodgkin lymphoma and primary mediastinal B-cell lymphoma
Panelist Lisa G. Roth, MD, of Weill Cornell Medicine, New York, reviewed the genomic landscape of Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL).
Dr. Roth explained that both HL and PMBCL are derived from thymic B cells, predominantly affect the mediastinum, and are CD30-positive lymphomas. Both are characterized by upregulation of JAK/STAT and NF-kappaB as well as overexpression of PD-L1.
Dr. Roth noted that HL is challenging to sequence by standard methods because Reed Sternberg (HRS) cells represent less than 1% of the cellular infiltrate. Recurrently mutated genes in HL cluster by histologic subtype.
Whole-exome sequencing of HRS cells show loss of beta-2 microglobulin and MHC-1 expression, HLA-B, NF-kappaB signaling, and JAK-STAT signaling, according to data published in Blood Advances in 2019.
Dr. Roth’s lab performed immunohistochemistry on tissue microarrays in 145 cases of HL (unpublished data). Results showed that loss of beta-2 microglobulin is more common in younger HL patients. For other alterations, there were too few cases to know.
Dr. Roth’s lab is a member of a pediatric/AYA HL sequencing multi-institutional consortium that has been able to extract DNA and RNA from samples submitted for whole-exome sequencing. The consortium’s goal is to shed light on implications of other genomic alterations that may differ by age in HL patients.
Dr. Roth cited research showing that PMBCL shares molecular alterations similar to those of HL. Alterations in PMBCL suggest dysregulated cellular signaling and immune evasion mechanisms (e.g., deletions in MHC type 1 and 2, beta-2 microglobulin, JAK-STAT, and NF-kappaB mutations) that provide opportunities to study novel agents, according to data published in Blood in 2019.
By early 2021, the S1826 and ANHL1931 studies, which have no age restriction, will be available to AYA lymphoma patients with HL and PMBCL, respectively, Dr. Roth said.
Follicular lymphoma: Clinical features by age
Panelist Abner Louissaint Jr, MD, PhD, of Massachusetts General Hospital in Boston, discussed age-related differences in follicular lymphoma (FL).
He noted that FL typically presents at an advanced stage, with low- or high-grade histology. It is increasingly common in adults in their 50s and 60s, representing 20% of all lymphomas. FL is rare in children and AYAs.
Dr. Louissaint explained that the typical flow cytometric findings in FL are BCL2 translocations, occurring in up to 85%-90% of low-grade and 50% of high-grade cases. The t(14;18)(q32;q21) translocation juxtaposes BCL2 on 18q21 to regulatory sequences and enhances the expression of elements of the Ig heavy chain.
Malignant cells in FL patients express CD20, CD10, CD21, and BCL2 (in contrast to normal germinal centers) and overexpress BCL6 (in contrast to normal follicles), Dr. Louissaint noted. He said the Ki-67 proliferative index of the malignant cells is typically low.
Pediatric-type FL is rare, but case series show clinical, pathologic, and molecular features that are distinctive from adult FL, Dr. Louissaint explained.
He then discussed the features of pediatric-type FL in multiple domains. In the clinical domain, there is a male predilection, and stage tends to be low. There is frequent involvement of nodes of the head and neck region and rare involvement of internal lymph node chains.
Pathologically, the malignant cells appear high grade, with architectural effacement, expansile follicular pattern, large lymphocyte size, and an elevated proliferation index. In contrast to adult FL, malignant cells in pediatric-type FL lack aberrant BCL2 expression.
Most importantly, for pediatric-type FL, the prognosis is excellent with durable remissions after surgical excision, Dr. Louissaint said.
Follicular lymphoma: Molecular features by age
Because of the excellent prognosis in pediatric-type FL, it is important to assess whether young adults with FL have adult-type or pediatric-type lesions, Dr. Louissaint said.
He cited many studies showing differences in adult and pediatric-type FL. In adult FL, the mutational landscape is characterized by frequent chromatin-modifying mutations in genes such as CREBBP, KM22D, and EP300.
In contrast, in pediatric-type FL, there are frequent activating MAPK pathway mutations, including mutations in the negative regulatory domain of MAP2K1. These mutations are not seen in adult FL.
Dr. Louissaint noted that there may be mutations in epigenetic modifiers (CREBBP, TNFRSF14) in both adult and pediatric-type FL. However, CREBBP is very unusual in pediatric-type FL and common in adult FL. This suggests the alterations in pediatric-type FL do not simply represent an early stage of the same disease as adult FL.
Despite a high proliferating fraction and absence of BCL2/BCL6/IRF4 rearrangements in pediatric-type FL, the presence of these features was associated with dramatic difference in progression-free survival, according to research published in Blood in 2012.
A distinct entity
In 2016, the World Health Organization recognized pediatric-type FL as a distinct entity, with the following diagnostic criteria (published in Blood):
- At least partial effacement of nodal architecture, expansile follicles, intermediate-size blastoid cells, and no component of diffuse large B-cell lymphoma.
- Immunohistochemistry showing BCL6 positivity, BCL2 negativity or weak positivity, and a high proliferative fraction.
- Genomic studies showing no BCL2 amplification.
- Clinical features of nodal disease in the head and neck region, early clinical stage, age younger than 40 years, typically in a male with no internal nodes involved.
When FL occurs in AYAs, the diagnostic findings of pediatric-type FL suggest the patient will do well with conservative management (e.g., excision alone), Dr. Louissaint noted.
Two sizes do not fit all
The strategies that have improved cancer outcomes since the 1970s for children and older adults have been much less successful for AYAs with cancer.
As an oncologic community, we should not allow the AYA gap to persist. As always, the solutions are likely to involve focused clinical research, education, and communication. Effort will need to be targeted specifically to the AYA population.
Since health-related mortality is high even when cancer-specific outcomes improve, adopting and maintaining a healthy lifestyle must be a key part of the discussion with these young patients.
The biologic differences associated with AYA lymphomas demand participation in clinical trials.
Oncologists should vigorously support removing impediments to the participation of AYAs in prospective clinical trials, stratified (but unrestricted) by age, with careful analysis of patient-reported outcomes, late adverse effects, and biospecimen collection.
As Dr. Kelly noted in the question-and-answer period, the Children’s Oncology Group has an existing biobank of paraffin-embedded tumor samples, DNA from lymphoma specimens, plasma, and sera with clinically annotated data that can be given to investigators upon request and justification.
Going beyond eligibility for clinical trials
Unfortunately, we will likely find that broadening eligibility criteria is the “low-hanging fruit.” There are protocol-, patient-, and physician-related obstacles, according to a review published in Cancer in 2019.
Patient-related obstacles include fear of toxicity, uncertainty about placebos, a steep learning curve for health literacy, insurance-related impediments, and other access-related issues.
Discussions will need to be tailored to the AYA population. Frank, early conversations about fertility, sexuality, financial hardship, career advancement, work-life balance, and cognitive risks may not only facilitate treatment planning but also encourage the trust that is essential for patients to enroll in trials.
The investment in time, multidisciplinary staff and physician involvement, and potential delays in treatment initiation may be painful and inconvenient, but the benefits for long-term health outcomes and personal-professional relationships will be gratifying beyond measure.
Dr. Smith disclosed relationships with Genentech/Roche, Celgene, TGTX, Karyopharm, Janssen, and Bantem. Dr. Roth disclosed relationships with Janssen, ADC Therapeutics, and Celgene. Dr. Kelly and Dr. Louissaint had no financial relationships to disclose.
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.
In the 1970s, cancer survival was poor for young children and older adults in the United States, as shown by data published in the Journal of the National Cancer Institute.
Great progress has been made since the 1970s, but improvements in outcome have been less impressive for cancer patients aged 15-39 years, as shown by research published in Cancer.
Patients aged 15-39 years have been designated by the National Institutes of Health (NIH) as “adolescents and young adults (AYAs),” and the lag in survival benefit has been termed “the AYA gap.”
The AYA gap persists in lymphoma patients, and an expert panel recently outlined differences between lymphoma in AYAs and lymphoma in other age groups.
The experts spoke at a special session of the AACR Virtual Meeting: Advances in Malignant Lymphoma moderated by Somali M. Smith, MD, of the University of Chicago.
Factors that contribute to the AYA gap
About 89,000 AYAs are diagnosed with cancer each year in the United States, according to data from the National Cancer Institute (NCI). Lymphomas and thyroid cancer are the most common cancers among younger AYAs, aged 15-24 years.
In a report commissioned by the NIH in 2006, many factors contributing to the AYA gap were identified. Chief among them were:
- Limitations in access to care.
- Delayed diagnosis.
- Inconsistency in treatment and follow-up.
- Long-term toxicity (fertility, second malignancies, and cardiovascular disease).
These factors compromise health-related survival, even when cancer-specific survival is improved.
Panelist Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., noted that there are additional unique challenges for AYAs with cancer. These include:
- Pubertal changes.
- Developmental transition to independence.
- Societal impediments such as insurance coverage and disparities in access to specialized centers.
- Psychosocial factors such as health literacy and adherence to treatment and follow-up.
Focusing on lymphoma specifically, Dr. Kelly noted that lymphoma biology differs across the age spectrum and by race and ethnicity. Both tumor and host factors require further study, she said.
Clinical trial access for AYAs
Dr. Kelly emphasized that, unfortunately, clinical research participation is low among AYAs. A major impediment is that adult clinical trials historically required participants to be at least 18 years old.
In addition, there has not been a focused effort to educate AYAs about regulatory safeguards to ensure safety and the promise of enhanced benefit to them in NCI Cancer Trials Network (NCTN) trials. As a result, the refusal rate is high.
A multi-stakeholder workshop, convened in May 2016 by the American Society of Clinical Oncology and Friends of Cancer Research, outlined opportunities for expanding trial eligibility to include children younger than 18 years in first-in-human and other adult cancer clinical trials, enhancing their access to new agents, without compromising safety.
Recently, collaborative efforts between the adult and children’s NCTN research groups have included AYAs in studies addressing cancers that span the age spectrum, including lymphoma.
However, as Dr. Kelly noted, there are differences in AYA lymphoid malignancy types with a transition from more pediatric to more adult types.
Hodgkin lymphoma and primary mediastinal B-cell lymphoma
Panelist Lisa G. Roth, MD, of Weill Cornell Medicine, New York, reviewed the genomic landscape of Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL).
Dr. Roth explained that both HL and PMBCL are derived from thymic B cells, predominantly affect the mediastinum, and are CD30-positive lymphomas. Both are characterized by upregulation of JAK/STAT and NF-kappaB as well as overexpression of PD-L1.
Dr. Roth noted that HL is challenging to sequence by standard methods because Reed Sternberg (HRS) cells represent less than 1% of the cellular infiltrate. Recurrently mutated genes in HL cluster by histologic subtype.
Whole-exome sequencing of HRS cells show loss of beta-2 microglobulin and MHC-1 expression, HLA-B, NF-kappaB signaling, and JAK-STAT signaling, according to data published in Blood Advances in 2019.
Dr. Roth’s lab performed immunohistochemistry on tissue microarrays in 145 cases of HL (unpublished data). Results showed that loss of beta-2 microglobulin is more common in younger HL patients. For other alterations, there were too few cases to know.
Dr. Roth’s lab is a member of a pediatric/AYA HL sequencing multi-institutional consortium that has been able to extract DNA and RNA from samples submitted for whole-exome sequencing. The consortium’s goal is to shed light on implications of other genomic alterations that may differ by age in HL patients.
Dr. Roth cited research showing that PMBCL shares molecular alterations similar to those of HL. Alterations in PMBCL suggest dysregulated cellular signaling and immune evasion mechanisms (e.g., deletions in MHC type 1 and 2, beta-2 microglobulin, JAK-STAT, and NF-kappaB mutations) that provide opportunities to study novel agents, according to data published in Blood in 2019.
By early 2021, the S1826 and ANHL1931 studies, which have no age restriction, will be available to AYA lymphoma patients with HL and PMBCL, respectively, Dr. Roth said.
Follicular lymphoma: Clinical features by age
Panelist Abner Louissaint Jr, MD, PhD, of Massachusetts General Hospital in Boston, discussed age-related differences in follicular lymphoma (FL).
He noted that FL typically presents at an advanced stage, with low- or high-grade histology. It is increasingly common in adults in their 50s and 60s, representing 20% of all lymphomas. FL is rare in children and AYAs.
Dr. Louissaint explained that the typical flow cytometric findings in FL are BCL2 translocations, occurring in up to 85%-90% of low-grade and 50% of high-grade cases. The t(14;18)(q32;q21) translocation juxtaposes BCL2 on 18q21 to regulatory sequences and enhances the expression of elements of the Ig heavy chain.
Malignant cells in FL patients express CD20, CD10, CD21, and BCL2 (in contrast to normal germinal centers) and overexpress BCL6 (in contrast to normal follicles), Dr. Louissaint noted. He said the Ki-67 proliferative index of the malignant cells is typically low.
Pediatric-type FL is rare, but case series show clinical, pathologic, and molecular features that are distinctive from adult FL, Dr. Louissaint explained.
He then discussed the features of pediatric-type FL in multiple domains. In the clinical domain, there is a male predilection, and stage tends to be low. There is frequent involvement of nodes of the head and neck region and rare involvement of internal lymph node chains.
Pathologically, the malignant cells appear high grade, with architectural effacement, expansile follicular pattern, large lymphocyte size, and an elevated proliferation index. In contrast to adult FL, malignant cells in pediatric-type FL lack aberrant BCL2 expression.
Most importantly, for pediatric-type FL, the prognosis is excellent with durable remissions after surgical excision, Dr. Louissaint said.
Follicular lymphoma: Molecular features by age
Because of the excellent prognosis in pediatric-type FL, it is important to assess whether young adults with FL have adult-type or pediatric-type lesions, Dr. Louissaint said.
He cited many studies showing differences in adult and pediatric-type FL. In adult FL, the mutational landscape is characterized by frequent chromatin-modifying mutations in genes such as CREBBP, KM22D, and EP300.
In contrast, in pediatric-type FL, there are frequent activating MAPK pathway mutations, including mutations in the negative regulatory domain of MAP2K1. These mutations are not seen in adult FL.
Dr. Louissaint noted that there may be mutations in epigenetic modifiers (CREBBP, TNFRSF14) in both adult and pediatric-type FL. However, CREBBP is very unusual in pediatric-type FL and common in adult FL. This suggests the alterations in pediatric-type FL do not simply represent an early stage of the same disease as adult FL.
Despite a high proliferating fraction and absence of BCL2/BCL6/IRF4 rearrangements in pediatric-type FL, the presence of these features was associated with dramatic difference in progression-free survival, according to research published in Blood in 2012.
A distinct entity
In 2016, the World Health Organization recognized pediatric-type FL as a distinct entity, with the following diagnostic criteria (published in Blood):
- At least partial effacement of nodal architecture, expansile follicles, intermediate-size blastoid cells, and no component of diffuse large B-cell lymphoma.
- Immunohistochemistry showing BCL6 positivity, BCL2 negativity or weak positivity, and a high proliferative fraction.
- Genomic studies showing no BCL2 amplification.
- Clinical features of nodal disease in the head and neck region, early clinical stage, age younger than 40 years, typically in a male with no internal nodes involved.
When FL occurs in AYAs, the diagnostic findings of pediatric-type FL suggest the patient will do well with conservative management (e.g., excision alone), Dr. Louissaint noted.
Two sizes do not fit all
The strategies that have improved cancer outcomes since the 1970s for children and older adults have been much less successful for AYAs with cancer.
As an oncologic community, we should not allow the AYA gap to persist. As always, the solutions are likely to involve focused clinical research, education, and communication. Effort will need to be targeted specifically to the AYA population.
Since health-related mortality is high even when cancer-specific outcomes improve, adopting and maintaining a healthy lifestyle must be a key part of the discussion with these young patients.
The biologic differences associated with AYA lymphomas demand participation in clinical trials.
Oncologists should vigorously support removing impediments to the participation of AYAs in prospective clinical trials, stratified (but unrestricted) by age, with careful analysis of patient-reported outcomes, late adverse effects, and biospecimen collection.
As Dr. Kelly noted in the question-and-answer period, the Children’s Oncology Group has an existing biobank of paraffin-embedded tumor samples, DNA from lymphoma specimens, plasma, and sera with clinically annotated data that can be given to investigators upon request and justification.
Going beyond eligibility for clinical trials
Unfortunately, we will likely find that broadening eligibility criteria is the “low-hanging fruit.” There are protocol-, patient-, and physician-related obstacles, according to a review published in Cancer in 2019.
Patient-related obstacles include fear of toxicity, uncertainty about placebos, a steep learning curve for health literacy, insurance-related impediments, and other access-related issues.
Discussions will need to be tailored to the AYA population. Frank, early conversations about fertility, sexuality, financial hardship, career advancement, work-life balance, and cognitive risks may not only facilitate treatment planning but also encourage the trust that is essential for patients to enroll in trials.
The investment in time, multidisciplinary staff and physician involvement, and potential delays in treatment initiation may be painful and inconvenient, but the benefits for long-term health outcomes and personal-professional relationships will be gratifying beyond measure.
Dr. Smith disclosed relationships with Genentech/Roche, Celgene, TGTX, Karyopharm, Janssen, and Bantem. Dr. Roth disclosed relationships with Janssen, ADC Therapeutics, and Celgene. Dr. Kelly and Dr. Louissaint had no financial relationships to disclose.
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.
In the 1970s, cancer survival was poor for young children and older adults in the United States, as shown by data published in the Journal of the National Cancer Institute.
Great progress has been made since the 1970s, but improvements in outcome have been less impressive for cancer patients aged 15-39 years, as shown by research published in Cancer.
Patients aged 15-39 years have been designated by the National Institutes of Health (NIH) as “adolescents and young adults (AYAs),” and the lag in survival benefit has been termed “the AYA gap.”
The AYA gap persists in lymphoma patients, and an expert panel recently outlined differences between lymphoma in AYAs and lymphoma in other age groups.
The experts spoke at a special session of the AACR Virtual Meeting: Advances in Malignant Lymphoma moderated by Somali M. Smith, MD, of the University of Chicago.
Factors that contribute to the AYA gap
About 89,000 AYAs are diagnosed with cancer each year in the United States, according to data from the National Cancer Institute (NCI). Lymphomas and thyroid cancer are the most common cancers among younger AYAs, aged 15-24 years.
In a report commissioned by the NIH in 2006, many factors contributing to the AYA gap were identified. Chief among them were:
- Limitations in access to care.
- Delayed diagnosis.
- Inconsistency in treatment and follow-up.
- Long-term toxicity (fertility, second malignancies, and cardiovascular disease).
These factors compromise health-related survival, even when cancer-specific survival is improved.
Panelist Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., noted that there are additional unique challenges for AYAs with cancer. These include:
- Pubertal changes.
- Developmental transition to independence.
- Societal impediments such as insurance coverage and disparities in access to specialized centers.
- Psychosocial factors such as health literacy and adherence to treatment and follow-up.
Focusing on lymphoma specifically, Dr. Kelly noted that lymphoma biology differs across the age spectrum and by race and ethnicity. Both tumor and host factors require further study, she said.
Clinical trial access for AYAs
Dr. Kelly emphasized that, unfortunately, clinical research participation is low among AYAs. A major impediment is that adult clinical trials historically required participants to be at least 18 years old.
In addition, there has not been a focused effort to educate AYAs about regulatory safeguards to ensure safety and the promise of enhanced benefit to them in NCI Cancer Trials Network (NCTN) trials. As a result, the refusal rate is high.
A multi-stakeholder workshop, convened in May 2016 by the American Society of Clinical Oncology and Friends of Cancer Research, outlined opportunities for expanding trial eligibility to include children younger than 18 years in first-in-human and other adult cancer clinical trials, enhancing their access to new agents, without compromising safety.
Recently, collaborative efforts between the adult and children’s NCTN research groups have included AYAs in studies addressing cancers that span the age spectrum, including lymphoma.
However, as Dr. Kelly noted, there are differences in AYA lymphoid malignancy types with a transition from more pediatric to more adult types.
Hodgkin lymphoma and primary mediastinal B-cell lymphoma
Panelist Lisa G. Roth, MD, of Weill Cornell Medicine, New York, reviewed the genomic landscape of Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL).
Dr. Roth explained that both HL and PMBCL are derived from thymic B cells, predominantly affect the mediastinum, and are CD30-positive lymphomas. Both are characterized by upregulation of JAK/STAT and NF-kappaB as well as overexpression of PD-L1.
Dr. Roth noted that HL is challenging to sequence by standard methods because Reed Sternberg (HRS) cells represent less than 1% of the cellular infiltrate. Recurrently mutated genes in HL cluster by histologic subtype.
Whole-exome sequencing of HRS cells show loss of beta-2 microglobulin and MHC-1 expression, HLA-B, NF-kappaB signaling, and JAK-STAT signaling, according to data published in Blood Advances in 2019.
Dr. Roth’s lab performed immunohistochemistry on tissue microarrays in 145 cases of HL (unpublished data). Results showed that loss of beta-2 microglobulin is more common in younger HL patients. For other alterations, there were too few cases to know.
Dr. Roth’s lab is a member of a pediatric/AYA HL sequencing multi-institutional consortium that has been able to extract DNA and RNA from samples submitted for whole-exome sequencing. The consortium’s goal is to shed light on implications of other genomic alterations that may differ by age in HL patients.
Dr. Roth cited research showing that PMBCL shares molecular alterations similar to those of HL. Alterations in PMBCL suggest dysregulated cellular signaling and immune evasion mechanisms (e.g., deletions in MHC type 1 and 2, beta-2 microglobulin, JAK-STAT, and NF-kappaB mutations) that provide opportunities to study novel agents, according to data published in Blood in 2019.
By early 2021, the S1826 and ANHL1931 studies, which have no age restriction, will be available to AYA lymphoma patients with HL and PMBCL, respectively, Dr. Roth said.
Follicular lymphoma: Clinical features by age
Panelist Abner Louissaint Jr, MD, PhD, of Massachusetts General Hospital in Boston, discussed age-related differences in follicular lymphoma (FL).
He noted that FL typically presents at an advanced stage, with low- or high-grade histology. It is increasingly common in adults in their 50s and 60s, representing 20% of all lymphomas. FL is rare in children and AYAs.
Dr. Louissaint explained that the typical flow cytometric findings in FL are BCL2 translocations, occurring in up to 85%-90% of low-grade and 50% of high-grade cases. The t(14;18)(q32;q21) translocation juxtaposes BCL2 on 18q21 to regulatory sequences and enhances the expression of elements of the Ig heavy chain.
Malignant cells in FL patients express CD20, CD10, CD21, and BCL2 (in contrast to normal germinal centers) and overexpress BCL6 (in contrast to normal follicles), Dr. Louissaint noted. He said the Ki-67 proliferative index of the malignant cells is typically low.
Pediatric-type FL is rare, but case series show clinical, pathologic, and molecular features that are distinctive from adult FL, Dr. Louissaint explained.
He then discussed the features of pediatric-type FL in multiple domains. In the clinical domain, there is a male predilection, and stage tends to be low. There is frequent involvement of nodes of the head and neck region and rare involvement of internal lymph node chains.
Pathologically, the malignant cells appear high grade, with architectural effacement, expansile follicular pattern, large lymphocyte size, and an elevated proliferation index. In contrast to adult FL, malignant cells in pediatric-type FL lack aberrant BCL2 expression.
Most importantly, for pediatric-type FL, the prognosis is excellent with durable remissions after surgical excision, Dr. Louissaint said.
Follicular lymphoma: Molecular features by age
Because of the excellent prognosis in pediatric-type FL, it is important to assess whether young adults with FL have adult-type or pediatric-type lesions, Dr. Louissaint said.
He cited many studies showing differences in adult and pediatric-type FL. In adult FL, the mutational landscape is characterized by frequent chromatin-modifying mutations in genes such as CREBBP, KM22D, and EP300.
In contrast, in pediatric-type FL, there are frequent activating MAPK pathway mutations, including mutations in the negative regulatory domain of MAP2K1. These mutations are not seen in adult FL.
Dr. Louissaint noted that there may be mutations in epigenetic modifiers (CREBBP, TNFRSF14) in both adult and pediatric-type FL. However, CREBBP is very unusual in pediatric-type FL and common in adult FL. This suggests the alterations in pediatric-type FL do not simply represent an early stage of the same disease as adult FL.
Despite a high proliferating fraction and absence of BCL2/BCL6/IRF4 rearrangements in pediatric-type FL, the presence of these features was associated with dramatic difference in progression-free survival, according to research published in Blood in 2012.
A distinct entity
In 2016, the World Health Organization recognized pediatric-type FL as a distinct entity, with the following diagnostic criteria (published in Blood):
- At least partial effacement of nodal architecture, expansile follicles, intermediate-size blastoid cells, and no component of diffuse large B-cell lymphoma.
- Immunohistochemistry showing BCL6 positivity, BCL2 negativity or weak positivity, and a high proliferative fraction.
- Genomic studies showing no BCL2 amplification.
- Clinical features of nodal disease in the head and neck region, early clinical stage, age younger than 40 years, typically in a male with no internal nodes involved.
When FL occurs in AYAs, the diagnostic findings of pediatric-type FL suggest the patient will do well with conservative management (e.g., excision alone), Dr. Louissaint noted.
Two sizes do not fit all
The strategies that have improved cancer outcomes since the 1970s for children and older adults have been much less successful for AYAs with cancer.
As an oncologic community, we should not allow the AYA gap to persist. As always, the solutions are likely to involve focused clinical research, education, and communication. Effort will need to be targeted specifically to the AYA population.
Since health-related mortality is high even when cancer-specific outcomes improve, adopting and maintaining a healthy lifestyle must be a key part of the discussion with these young patients.
The biologic differences associated with AYA lymphomas demand participation in clinical trials.
Oncologists should vigorously support removing impediments to the participation of AYAs in prospective clinical trials, stratified (but unrestricted) by age, with careful analysis of patient-reported outcomes, late adverse effects, and biospecimen collection.
As Dr. Kelly noted in the question-and-answer period, the Children’s Oncology Group has an existing biobank of paraffin-embedded tumor samples, DNA from lymphoma specimens, plasma, and sera with clinically annotated data that can be given to investigators upon request and justification.
Going beyond eligibility for clinical trials
Unfortunately, we will likely find that broadening eligibility criteria is the “low-hanging fruit.” There are protocol-, patient-, and physician-related obstacles, according to a review published in Cancer in 2019.
Patient-related obstacles include fear of toxicity, uncertainty about placebos, a steep learning curve for health literacy, insurance-related impediments, and other access-related issues.
Discussions will need to be tailored to the AYA population. Frank, early conversations about fertility, sexuality, financial hardship, career advancement, work-life balance, and cognitive risks may not only facilitate treatment planning but also encourage the trust that is essential for patients to enroll in trials.
The investment in time, multidisciplinary staff and physician involvement, and potential delays in treatment initiation may be painful and inconvenient, but the benefits for long-term health outcomes and personal-professional relationships will be gratifying beyond measure.
Dr. Smith disclosed relationships with Genentech/Roche, Celgene, TGTX, Karyopharm, Janssen, and Bantem. Dr. Roth disclosed relationships with Janssen, ADC Therapeutics, and Celgene. Dr. Kelly and Dr. Louissaint had no financial relationships to disclose.
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.
FROM AACR ADVANCES IN MALIGNANT LYMPHOMA 2020
Survey quantifies COVID-19’s impact on oncology
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
FROM ESMO 2020
Hepatitis screening now for all patients with cancer on therapy
All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.
“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.
Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.
The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.
“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.
“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.
The updated opinion was published online July 27 in the Journal of Clinical Oncology.
It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.
ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.
The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.
“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.
The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.
Anticancer therapy should not be delayed pending the results, they write.
Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.
Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.
Challenges in implementing universal HBV screening
The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.
In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.
A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.
“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”
The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.
Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.
“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.
Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.
“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.
Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.
He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.
More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”
Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.
If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.
However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.
The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”
The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.
Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.
This article first appeared on Medscape.com.
All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.
“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.
Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.
The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.
“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.
“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.
The updated opinion was published online July 27 in the Journal of Clinical Oncology.
It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.
ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.
The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.
“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.
The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.
Anticancer therapy should not be delayed pending the results, they write.
Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.
Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.
Challenges in implementing universal HBV screening
The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.
In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.
A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.
“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”
The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.
Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.
“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.
Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.
“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.
Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.
He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.
More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”
Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.
If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.
However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.
The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”
The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.
Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.
This article first appeared on Medscape.com.
All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.
“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.
Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.
The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.
“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.
“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.
The updated opinion was published online July 27 in the Journal of Clinical Oncology.
It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.
ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.
The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.
“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.
The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.
Anticancer therapy should not be delayed pending the results, they write.
Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.
Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.
Challenges in implementing universal HBV screening
The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.
In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.
A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.
“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”
The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.
Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.
“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.
Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.
“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.
Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.
He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.
More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”
Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.
If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.
However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.
The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”
The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.
Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.
This article first appeared on Medscape.com.