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In a session at the annual meeting of the American Society of Hematology in December, clinicians defined the extent of the problem — which one described as a “survival cliff” — and they discussed potential strategies to turn things around.
Cleveland Clinic hematologist John Molina, MD, EdM, highlighted a 2022 study that revealed “the 5-year overall survival for younger pediatric patients is quite phenomenal at 93%. But as you start shifting even to 15-19 patients, that shifts to an overall survival of 74%.”
In the rest of the young adult population, from age 20 to 39, the overall survival rate dips down to 59%. What’s going on?
As Dr. Molina noted, a 2008 study revealed that outcomes in ALL for those aged 16-20 “historically depended on which door you walked into”: the pediatric setting or the adult setting. Patients fared better on pediatric regimens.
Currently, he explained, those who begin treatment in adult oncology clinics will start with either a pediatric-inspired treatment called CALGB 10403 or HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone plus methotrexate and cytarabine).
CALGB 10403 was developed based on a pediatric backbone of COG AALL0232, Dr. Molina said, and has higher doses of major myelosuppressive agents vs. HyperCVAD. A 2019 study determined that it was feasible to treat adolescents and young adults up to age 40 “with low treatment-related mortality and marked improvement in outcomes. OS [overall survival] at 3 years was 73%.”
However, Dr. Molina observed that only 39% of patients completed the treatment per protocol.
Which is better, CALGB 10403 or HyperCVAD? Dr. Molina said the risk of infertility and other long-term adverse effects is higher in HyperCVAD, but it has a lower risk of hepatic, pancreatic and thrombotic complications. And the CALGB 10403 regimen is more complicated to deliver, which is a potential obstacle in clinics without large numbers of patients.
As for outcomes, some research suggests they improve with pediatric-inspired regimens like CALGB 10403, he said, noting that “the debate continues.”
However, even with better regimens, Dr. Molina added, older ALL patients are still faring worse.
Also at the ASH presentation, Emory University/Children’s Healthcare of Atlanta pediatric cancer specialist Tamara Miller, MD, explored possible reasons that could explain the difference in outcomes based on age.
Cancer biology, response to chemotherapy, toxicities, psychosocial challenges, and low enrollment in clinical trials are all potential factors, she said. Specifically, aging into adulthood can lower tolerance of chemotherapy, and older patients are more prone to obesity, which is associated with worse outcomes, she said.
As for psychosocial challenges, it can be hard for older patients to manage their own medications, and they may lack insurance coverage, she said. Some patients may have worries about fertility, she added, and some may rebel against the requirements of treatment. Adherence is crucial to reducing risk of relapse, she added.
University of Cincinnati leukemia specialist Emily Curran, MD, told the ASH audience that researchers are exploring various avenues to improve outcomes.
Philadelphia chromosome-like (Ph-like) ALL, a subset of B-ALL, is associated with worse outcomes, she said, but it has multiple targetable pathways. An ongoing trial is exploring ruxolitinib (Jakafi) and chemotherapy in patients aged 18-39 with Ph-like ALL, Dr. Curran said.
Researchers are also wondering if up-front immunotherapy can help overcome disease biology, she said. Another potential therapy, she added, is CAR-T therapy for T-ALL.
Beyond cancer biology, “psychosocial factors are an even more challenging area in which we have fewer ongoing and less solutions,” Dr. Curran said.
Dr. Molina disclosed honoraria and consulting relationships with Autolus. Dr. Curran reported ties with Kite, Amgen, Incyte, Pfizer, Jazz, and Servier. Dr. Miller has no disclosures.
In a session at the annual meeting of the American Society of Hematology in December, clinicians defined the extent of the problem — which one described as a “survival cliff” — and they discussed potential strategies to turn things around.
Cleveland Clinic hematologist John Molina, MD, EdM, highlighted a 2022 study that revealed “the 5-year overall survival for younger pediatric patients is quite phenomenal at 93%. But as you start shifting even to 15-19 patients, that shifts to an overall survival of 74%.”
In the rest of the young adult population, from age 20 to 39, the overall survival rate dips down to 59%. What’s going on?
As Dr. Molina noted, a 2008 study revealed that outcomes in ALL for those aged 16-20 “historically depended on which door you walked into”: the pediatric setting or the adult setting. Patients fared better on pediatric regimens.
Currently, he explained, those who begin treatment in adult oncology clinics will start with either a pediatric-inspired treatment called CALGB 10403 or HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone plus methotrexate and cytarabine).
CALGB 10403 was developed based on a pediatric backbone of COG AALL0232, Dr. Molina said, and has higher doses of major myelosuppressive agents vs. HyperCVAD. A 2019 study determined that it was feasible to treat adolescents and young adults up to age 40 “with low treatment-related mortality and marked improvement in outcomes. OS [overall survival] at 3 years was 73%.”
However, Dr. Molina observed that only 39% of patients completed the treatment per protocol.
Which is better, CALGB 10403 or HyperCVAD? Dr. Molina said the risk of infertility and other long-term adverse effects is higher in HyperCVAD, but it has a lower risk of hepatic, pancreatic and thrombotic complications. And the CALGB 10403 regimen is more complicated to deliver, which is a potential obstacle in clinics without large numbers of patients.
As for outcomes, some research suggests they improve with pediatric-inspired regimens like CALGB 10403, he said, noting that “the debate continues.”
However, even with better regimens, Dr. Molina added, older ALL patients are still faring worse.
Also at the ASH presentation, Emory University/Children’s Healthcare of Atlanta pediatric cancer specialist Tamara Miller, MD, explored possible reasons that could explain the difference in outcomes based on age.
Cancer biology, response to chemotherapy, toxicities, psychosocial challenges, and low enrollment in clinical trials are all potential factors, she said. Specifically, aging into adulthood can lower tolerance of chemotherapy, and older patients are more prone to obesity, which is associated with worse outcomes, she said.
As for psychosocial challenges, it can be hard for older patients to manage their own medications, and they may lack insurance coverage, she said. Some patients may have worries about fertility, she added, and some may rebel against the requirements of treatment. Adherence is crucial to reducing risk of relapse, she added.
University of Cincinnati leukemia specialist Emily Curran, MD, told the ASH audience that researchers are exploring various avenues to improve outcomes.
Philadelphia chromosome-like (Ph-like) ALL, a subset of B-ALL, is associated with worse outcomes, she said, but it has multiple targetable pathways. An ongoing trial is exploring ruxolitinib (Jakafi) and chemotherapy in patients aged 18-39 with Ph-like ALL, Dr. Curran said.
Researchers are also wondering if up-front immunotherapy can help overcome disease biology, she said. Another potential therapy, she added, is CAR-T therapy for T-ALL.
Beyond cancer biology, “psychosocial factors are an even more challenging area in which we have fewer ongoing and less solutions,” Dr. Curran said.
Dr. Molina disclosed honoraria and consulting relationships with Autolus. Dr. Curran reported ties with Kite, Amgen, Incyte, Pfizer, Jazz, and Servier. Dr. Miller has no disclosures.
In a session at the annual meeting of the American Society of Hematology in December, clinicians defined the extent of the problem — which one described as a “survival cliff” — and they discussed potential strategies to turn things around.
Cleveland Clinic hematologist John Molina, MD, EdM, highlighted a 2022 study that revealed “the 5-year overall survival for younger pediatric patients is quite phenomenal at 93%. But as you start shifting even to 15-19 patients, that shifts to an overall survival of 74%.”
In the rest of the young adult population, from age 20 to 39, the overall survival rate dips down to 59%. What’s going on?
As Dr. Molina noted, a 2008 study revealed that outcomes in ALL for those aged 16-20 “historically depended on which door you walked into”: the pediatric setting or the adult setting. Patients fared better on pediatric regimens.
Currently, he explained, those who begin treatment in adult oncology clinics will start with either a pediatric-inspired treatment called CALGB 10403 or HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone plus methotrexate and cytarabine).
CALGB 10403 was developed based on a pediatric backbone of COG AALL0232, Dr. Molina said, and has higher doses of major myelosuppressive agents vs. HyperCVAD. A 2019 study determined that it was feasible to treat adolescents and young adults up to age 40 “with low treatment-related mortality and marked improvement in outcomes. OS [overall survival] at 3 years was 73%.”
However, Dr. Molina observed that only 39% of patients completed the treatment per protocol.
Which is better, CALGB 10403 or HyperCVAD? Dr. Molina said the risk of infertility and other long-term adverse effects is higher in HyperCVAD, but it has a lower risk of hepatic, pancreatic and thrombotic complications. And the CALGB 10403 regimen is more complicated to deliver, which is a potential obstacle in clinics without large numbers of patients.
As for outcomes, some research suggests they improve with pediatric-inspired regimens like CALGB 10403, he said, noting that “the debate continues.”
However, even with better regimens, Dr. Molina added, older ALL patients are still faring worse.
Also at the ASH presentation, Emory University/Children’s Healthcare of Atlanta pediatric cancer specialist Tamara Miller, MD, explored possible reasons that could explain the difference in outcomes based on age.
Cancer biology, response to chemotherapy, toxicities, psychosocial challenges, and low enrollment in clinical trials are all potential factors, she said. Specifically, aging into adulthood can lower tolerance of chemotherapy, and older patients are more prone to obesity, which is associated with worse outcomes, she said.
As for psychosocial challenges, it can be hard for older patients to manage their own medications, and they may lack insurance coverage, she said. Some patients may have worries about fertility, she added, and some may rebel against the requirements of treatment. Adherence is crucial to reducing risk of relapse, she added.
University of Cincinnati leukemia specialist Emily Curran, MD, told the ASH audience that researchers are exploring various avenues to improve outcomes.
Philadelphia chromosome-like (Ph-like) ALL, a subset of B-ALL, is associated with worse outcomes, she said, but it has multiple targetable pathways. An ongoing trial is exploring ruxolitinib (Jakafi) and chemotherapy in patients aged 18-39 with Ph-like ALL, Dr. Curran said.
Researchers are also wondering if up-front immunotherapy can help overcome disease biology, she said. Another potential therapy, she added, is CAR-T therapy for T-ALL.
Beyond cancer biology, “psychosocial factors are an even more challenging area in which we have fewer ongoing and less solutions,” Dr. Curran said.
Dr. Molina disclosed honoraria and consulting relationships with Autolus. Dr. Curran reported ties with Kite, Amgen, Incyte, Pfizer, Jazz, and Servier. Dr. Miller has no disclosures.
FROM ASH 2023