TBD Meeting (3270-23)

SAN DIEGO — It’s one of the great mysteries of hematology: Why do children with acute lymphoblastic leukemia (ALL) fare well in the modern era of cancer treatment, while adolescents and younger adults continue to face stubbornly high mortality rates?

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.

SAN DIEGO — It’s one of the great mysteries of hematology: Why do children with acute lymphoblastic leukemia (ALL) fare well in the modern era of cancer treatment, while adolescents and younger adults continue to face stubbornly high mortality rates?

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.

SAN DIEGO — It’s one of the great mysteries of hematology: Why do children with acute lymphoblastic leukemia (ALL) fare well in the modern era of cancer treatment, while adolescents and younger adults continue to face stubbornly high mortality rates?

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.

SAN DIEGO — Clinicians are encountering unique challenges as the American Society of Hematology (ASH) develops the first-ever clinical practice guidelines for treating acute lymphocytic leukemia (ALL) in adolescents and young adults, a wide-ranging age span that runs from older teenagers to thirtysomethings on the cusp of middle age.

At the crux of the matter is the unusual nature of ALL, said University of Chicago leukemia specialist Wendy Stock, MD, in a presentation at the annual meeting of the American Society of Hematology in December 2023. The disease is both rare and unique since it spans the entire lifetime from infancy to old age, she said.

The guidelines will focus on adolescents and young adults, which the National Cancer Institute defines as those aged 15-39. For these patients, “treatment is administered by the whole gamut of practitioners in the world of hematology, from pediatricians to adult hematologist/oncologists, which provides unique challenges in terms of understanding and access to care,” Dr. Stock said.

As she explained, ALL “is the bread and butter of pediatric oncology, but in the world of adult hematology-oncology, many patients are treated in small-practice settings where there have been very few uniform approaches available to the treating practitioners,” she said. “There’s not going to ever be the ability to get every — or even the majority — of adults into those big academic centers.”

Meanwhile, research from around the world has highlighted major mortality gaps between pediatric and adult care in ALL. “This has been our huge challenge: Is it the treatment approach? Is it the disease biology, the patient biology, the doctors who treat these diseases? Is it the geographic location where they’re treated? Well, we now know that, of course, it’s probably all of the above, and a lot more than that.”

In light of the need for guidance in ALL treatment, it will be crucial to disseminate data and recommendations via the guidelines, she said.

In 2021, ASH members approved the development of new clinical practice guidelines for this population. The process so far has been difficult, said pediatric oncologist Sumit Gupta, MD, PhD, of the Hospital for Sick Children in Toronto, Ontario, at the ASH presentation.

“At one point,” Dr. Gupta recalled, “someone on our methodology team said this was the most challenging systematic review and guideline creation that they’d ever worked on, which is not what you want to hear as a co-chair.”

One major challenge for the guideline drafters is to balance ALL research findings that cover only certain ages, Dr. Gupta said. A study, for example, may only include patients up to age 21 or over age 35, making it difficult to decide how it fits into a larger evidence base for adolescents and young adults.

“We don’t always have perfect evidence. But we’re trying to take all of that and translate it into a formalized systematic review,” he said. “This is tricky for any guideline. But ALL poses a particular challenge because of how the evidence base is spread out.”

Another challenge is figuring out how to review psychosocial interventions in ALL. They are obviously crucial, he said. But should guidelines only take into account strategies that were tested in ALL? Or should they look at a wider perspective and encompass research into non–ALL-specific approaches?

In terms of guidance about frontline treatment, the guideline developers are focusing on several topics, said University of Rochester hematologist/oncologist Kristen O’Dwyer, MD, at the ASH presentation. These include: Should adolescents and young adults receive pediatric or adult regimens? Where do targeted therapy, immunotherapy, steroids, allogeneic stem cell transplants, and central nervous system (CNS) prophylaxis fit in?

“Finally, there are a series of questions that are addressing the toxicity prevention and management that go along with these intensive chemotherapy regimens,” she said.

On one front, there’s a “knowledge gap” about the value of stem cell transplant vs pediatric-inspired chemotherapy as postremission therapies, Dr. O’Dwyer said, because there are no direct comparisons. What to do? “There are retrospective comparisons that are emerging along with population-level analysis, single-arm observational studies that suggest that a pediatric-based chemotherapy approach is superior with similar relapse rates and less treatment-related mortality,” she said.

ASH expects to release a draft of its ALL guidelines for adolescents and young adults later this year and publish final recommendations in late 2024 or early 2025.

Dr. Stock, Dr. Gupta, and Dr. O’Dwyer have no disclosures.

SAN DIEGO — Clinicians are encountering unique challenges as the American Society of Hematology (ASH) develops the first-ever clinical practice guidelines for treating acute lymphocytic leukemia (ALL) in adolescents and young adults, a wide-ranging age span that runs from older teenagers to thirtysomethings on the cusp of middle age.

At the crux of the matter is the unusual nature of ALL, said University of Chicago leukemia specialist Wendy Stock, MD, in a presentation at the annual meeting of the American Society of Hematology in December 2023. The disease is both rare and unique since it spans the entire lifetime from infancy to old age, she said.

The guidelines will focus on adolescents and young adults, which the National Cancer Institute defines as those aged 15-39. For these patients, “treatment is administered by the whole gamut of practitioners in the world of hematology, from pediatricians to adult hematologist/oncologists, which provides unique challenges in terms of understanding and access to care,” Dr. Stock said.

As she explained, ALL “is the bread and butter of pediatric oncology, but in the world of adult hematology-oncology, many patients are treated in small-practice settings where there have been very few uniform approaches available to the treating practitioners,” she said. “There’s not going to ever be the ability to get every — or even the majority — of adults into those big academic centers.”

Meanwhile, research from around the world has highlighted major mortality gaps between pediatric and adult care in ALL. “This has been our huge challenge: Is it the treatment approach? Is it the disease biology, the patient biology, the doctors who treat these diseases? Is it the geographic location where they’re treated? Well, we now know that, of course, it’s probably all of the above, and a lot more than that.”

In light of the need for guidance in ALL treatment, it will be crucial to disseminate data and recommendations via the guidelines, she said.

In 2021, ASH members approved the development of new clinical practice guidelines for this population. The process so far has been difficult, said pediatric oncologist Sumit Gupta, MD, PhD, of the Hospital for Sick Children in Toronto, Ontario, at the ASH presentation.

“At one point,” Dr. Gupta recalled, “someone on our methodology team said this was the most challenging systematic review and guideline creation that they’d ever worked on, which is not what you want to hear as a co-chair.”

One major challenge for the guideline drafters is to balance ALL research findings that cover only certain ages, Dr. Gupta said. A study, for example, may only include patients up to age 21 or over age 35, making it difficult to decide how it fits into a larger evidence base for adolescents and young adults.

“We don’t always have perfect evidence. But we’re trying to take all of that and translate it into a formalized systematic review,” he said. “This is tricky for any guideline. But ALL poses a particular challenge because of how the evidence base is spread out.”

Another challenge is figuring out how to review psychosocial interventions in ALL. They are obviously crucial, he said. But should guidelines only take into account strategies that were tested in ALL? Or should they look at a wider perspective and encompass research into non–ALL-specific approaches?

In terms of guidance about frontline treatment, the guideline developers are focusing on several topics, said University of Rochester hematologist/oncologist Kristen O’Dwyer, MD, at the ASH presentation. These include: Should adolescents and young adults receive pediatric or adult regimens? Where do targeted therapy, immunotherapy, steroids, allogeneic stem cell transplants, and central nervous system (CNS) prophylaxis fit in?

“Finally, there are a series of questions that are addressing the toxicity prevention and management that go along with these intensive chemotherapy regimens,” she said.

On one front, there’s a “knowledge gap” about the value of stem cell transplant vs pediatric-inspired chemotherapy as postremission therapies, Dr. O’Dwyer said, because there are no direct comparisons. What to do? “There are retrospective comparisons that are emerging along with population-level analysis, single-arm observational studies that suggest that a pediatric-based chemotherapy approach is superior with similar relapse rates and less treatment-related mortality,” she said.

ASH expects to release a draft of its ALL guidelines for adolescents and young adults later this year and publish final recommendations in late 2024 or early 2025.

Dr. Stock, Dr. Gupta, and Dr. O’Dwyer have no disclosures.

SAN DIEGO — Clinicians are encountering unique challenges as the American Society of Hematology (ASH) develops the first-ever clinical practice guidelines for treating acute lymphocytic leukemia (ALL) in adolescents and young adults, a wide-ranging age span that runs from older teenagers to thirtysomethings on the cusp of middle age.

At the crux of the matter is the unusual nature of ALL, said University of Chicago leukemia specialist Wendy Stock, MD, in a presentation at the annual meeting of the American Society of Hematology in December 2023. The disease is both rare and unique since it spans the entire lifetime from infancy to old age, she said.

The guidelines will focus on adolescents and young adults, which the National Cancer Institute defines as those aged 15-39. For these patients, “treatment is administered by the whole gamut of practitioners in the world of hematology, from pediatricians to adult hematologist/oncologists, which provides unique challenges in terms of understanding and access to care,” Dr. Stock said.

As she explained, ALL “is the bread and butter of pediatric oncology, but in the world of adult hematology-oncology, many patients are treated in small-practice settings where there have been very few uniform approaches available to the treating practitioners,” she said. “There’s not going to ever be the ability to get every — or even the majority — of adults into those big academic centers.”

Meanwhile, research from around the world has highlighted major mortality gaps between pediatric and adult care in ALL. “This has been our huge challenge: Is it the treatment approach? Is it the disease biology, the patient biology, the doctors who treat these diseases? Is it the geographic location where they’re treated? Well, we now know that, of course, it’s probably all of the above, and a lot more than that.”

In light of the need for guidance in ALL treatment, it will be crucial to disseminate data and recommendations via the guidelines, she said.

In 2021, ASH members approved the development of new clinical practice guidelines for this population. The process so far has been difficult, said pediatric oncologist Sumit Gupta, MD, PhD, of the Hospital for Sick Children in Toronto, Ontario, at the ASH presentation.

“At one point,” Dr. Gupta recalled, “someone on our methodology team said this was the most challenging systematic review and guideline creation that they’d ever worked on, which is not what you want to hear as a co-chair.”

One major challenge for the guideline drafters is to balance ALL research findings that cover only certain ages, Dr. Gupta said. A study, for example, may only include patients up to age 21 or over age 35, making it difficult to decide how it fits into a larger evidence base for adolescents and young adults.

“We don’t always have perfect evidence. But we’re trying to take all of that and translate it into a formalized systematic review,” he said. “This is tricky for any guideline. But ALL poses a particular challenge because of how the evidence base is spread out.”

Another challenge is figuring out how to review psychosocial interventions in ALL. They are obviously crucial, he said. But should guidelines only take into account strategies that were tested in ALL? Or should they look at a wider perspective and encompass research into non–ALL-specific approaches?

In terms of guidance about frontline treatment, the guideline developers are focusing on several topics, said University of Rochester hematologist/oncologist Kristen O’Dwyer, MD, at the ASH presentation. These include: Should adolescents and young adults receive pediatric or adult regimens? Where do targeted therapy, immunotherapy, steroids, allogeneic stem cell transplants, and central nervous system (CNS) prophylaxis fit in?

“Finally, there are a series of questions that are addressing the toxicity prevention and management that go along with these intensive chemotherapy regimens,” she said.

On one front, there’s a “knowledge gap” about the value of stem cell transplant vs pediatric-inspired chemotherapy as postremission therapies, Dr. O’Dwyer said, because there are no direct comparisons. What to do? “There are retrospective comparisons that are emerging along with population-level analysis, single-arm observational studies that suggest that a pediatric-based chemotherapy approach is superior with similar relapse rates and less treatment-related mortality,” she said.

ASH expects to release a draft of its ALL guidelines for adolescents and young adults later this year and publish final recommendations in late 2024 or early 2025.

Dr. Stock, Dr. Gupta, and Dr. O’Dwyer have no disclosures.

SAN DIEGO — While medicine has made tremendous strides against acute lymphoblastic leukemia (ALL) in children in recent years, a new study finds that mortality outcomes in older adults in the United States haven’t improved since the turn of the 21st century.

From 1999 to 2020, age-adjusted mortality rates for patients with ALL aged 55 and up didn’t change, oncologist-hematologist Jamie L. Koprivnikar, MD, of New Jersey’s Hackensack University Medical Center, reported at the annual meeting of the American Society of Hematology. The rates were 10.8 per 1 million in 1999 and 10.6 per 1 million in 2020.

By contrast, the mortality rates for children aged 0-15 improved from 3.5 per 1 million in 1999 to 2.2 per 1 million in 2020.

“The findings were particularly surprising and disappointing to me,” Dr. Koprivnikar said in an interview. “My overall sense is that we’ve really improved our outcomes of treating patients with ALL and are making great strides forward, moving away from so much chemotherapy and toward more kinds of immunotherapies and targeted therapies. So we need to understand what’s driving this.”

According to Dr. Koprivnikar, ALL is more common in children than adults. However, “even though the majority of cases tend to occur in children, we know that the majority of deaths are actually in the adult patient population,” she said.

One challenge for treatment is that therapies that work well in the pediatric population aren’t as effective in adults, she said. ALL is biologically different in adults in some ways, she added, and older patients may have more comorbidities. “It ends up being a really complicated story with all of these different factors playing into the complexity.”

For the new study, Dr. Koprivnikar and colleagues analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database. They found that 17,238 people died from ALL between 1999 and 2020. There were no significant differences in terms of gender, race, and region.

The study authors noted that mortality rates didn’t change despite medical advances in ALL such as blinatumomab, inotuzumab, and targeted tyrosine kinase inhibitor-based therapy. It’s unclear if the treatments have made it to the older-adult setting yet, Dr. Koprivnikar said.

There may be problems with access due to socioeconomic factors as well, she said. “ALL is actually more common among those of Hispanic heritage, and we don’t completely understand that.”

Marlise R. Luskin, MD, a leukemia specialist at Dana-Farber Cancer Institute, Boston, said in an interview that the study “is a reminder that clinical trial outcomes are limited — specifically trial results that often emphasize early results and report on a select population of older patients who generally are socially resourced and physically and mentally more fit.”

Dr. Luskin added that the study reports on outcomes through 2020, including years when newer regimens were not broadly disseminated outside of clinical trials.

Moving forward, she said, “this report suggests we need to continue to develop novel approaches and understand long-term outcomes as well as ‘real world’ outcomes. A similar study should be repeated again in 3-5 years as novel regimens become standard. We hope to see improvements.”

No study funding was reported. Dr. Koprivnikar disclosed consulting relationships with Alexion, GSK, Novartis, and Apellis. Other authors reported no disclosures. Dr. Luskin disclosed ties with Pfizer, Novartis, Jazz, Kite, and AbbVie.

SAN DIEGO — While medicine has made tremendous strides against acute lymphoblastic leukemia (ALL) in children in recent years, a new study finds that mortality outcomes in older adults in the United States haven’t improved since the turn of the 21st century.

From 1999 to 2020, age-adjusted mortality rates for patients with ALL aged 55 and up didn’t change, oncologist-hematologist Jamie L. Koprivnikar, MD, of New Jersey’s Hackensack University Medical Center, reported at the annual meeting of the American Society of Hematology. The rates were 10.8 per 1 million in 1999 and 10.6 per 1 million in 2020.

By contrast, the mortality rates for children aged 0-15 improved from 3.5 per 1 million in 1999 to 2.2 per 1 million in 2020.

“The findings were particularly surprising and disappointing to me,” Dr. Koprivnikar said in an interview. “My overall sense is that we’ve really improved our outcomes of treating patients with ALL and are making great strides forward, moving away from so much chemotherapy and toward more kinds of immunotherapies and targeted therapies. So we need to understand what’s driving this.”

According to Dr. Koprivnikar, ALL is more common in children than adults. However, “even though the majority of cases tend to occur in children, we know that the majority of deaths are actually in the adult patient population,” she said.

One challenge for treatment is that therapies that work well in the pediatric population aren’t as effective in adults, she said. ALL is biologically different in adults in some ways, she added, and older patients may have more comorbidities. “It ends up being a really complicated story with all of these different factors playing into the complexity.”

For the new study, Dr. Koprivnikar and colleagues analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database. They found that 17,238 people died from ALL between 1999 and 2020. There were no significant differences in terms of gender, race, and region.

The study authors noted that mortality rates didn’t change despite medical advances in ALL such as blinatumomab, inotuzumab, and targeted tyrosine kinase inhibitor-based therapy. It’s unclear if the treatments have made it to the older-adult setting yet, Dr. Koprivnikar said.

There may be problems with access due to socioeconomic factors as well, she said. “ALL is actually more common among those of Hispanic heritage, and we don’t completely understand that.”

Marlise R. Luskin, MD, a leukemia specialist at Dana-Farber Cancer Institute, Boston, said in an interview that the study “is a reminder that clinical trial outcomes are limited — specifically trial results that often emphasize early results and report on a select population of older patients who generally are socially resourced and physically and mentally more fit.”

Dr. Luskin added that the study reports on outcomes through 2020, including years when newer regimens were not broadly disseminated outside of clinical trials.

Moving forward, she said, “this report suggests we need to continue to develop novel approaches and understand long-term outcomes as well as ‘real world’ outcomes. A similar study should be repeated again in 3-5 years as novel regimens become standard. We hope to see improvements.”

No study funding was reported. Dr. Koprivnikar disclosed consulting relationships with Alexion, GSK, Novartis, and Apellis. Other authors reported no disclosures. Dr. Luskin disclosed ties with Pfizer, Novartis, Jazz, Kite, and AbbVie.

SAN DIEGO — While medicine has made tremendous strides against acute lymphoblastic leukemia (ALL) in children in recent years, a new study finds that mortality outcomes in older adults in the United States haven’t improved since the turn of the 21st century.

From 1999 to 2020, age-adjusted mortality rates for patients with ALL aged 55 and up didn’t change, oncologist-hematologist Jamie L. Koprivnikar, MD, of New Jersey’s Hackensack University Medical Center, reported at the annual meeting of the American Society of Hematology. The rates were 10.8 per 1 million in 1999 and 10.6 per 1 million in 2020.

By contrast, the mortality rates for children aged 0-15 improved from 3.5 per 1 million in 1999 to 2.2 per 1 million in 2020.

“The findings were particularly surprising and disappointing to me,” Dr. Koprivnikar said in an interview. “My overall sense is that we’ve really improved our outcomes of treating patients with ALL and are making great strides forward, moving away from so much chemotherapy and toward more kinds of immunotherapies and targeted therapies. So we need to understand what’s driving this.”

According to Dr. Koprivnikar, ALL is more common in children than adults. However, “even though the majority of cases tend to occur in children, we know that the majority of deaths are actually in the adult patient population,” she said.

One challenge for treatment is that therapies that work well in the pediatric population aren’t as effective in adults, she said. ALL is biologically different in adults in some ways, she added, and older patients may have more comorbidities. “It ends up being a really complicated story with all of these different factors playing into the complexity.”

For the new study, Dr. Koprivnikar and colleagues analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database. They found that 17,238 people died from ALL between 1999 and 2020. There were no significant differences in terms of gender, race, and region.

The study authors noted that mortality rates didn’t change despite medical advances in ALL such as blinatumomab, inotuzumab, and targeted tyrosine kinase inhibitor-based therapy. It’s unclear if the treatments have made it to the older-adult setting yet, Dr. Koprivnikar said.

There may be problems with access due to socioeconomic factors as well, she said. “ALL is actually more common among those of Hispanic heritage, and we don’t completely understand that.”

Marlise R. Luskin, MD, a leukemia specialist at Dana-Farber Cancer Institute, Boston, said in an interview that the study “is a reminder that clinical trial outcomes are limited — specifically trial results that often emphasize early results and report on a select population of older patients who generally are socially resourced and physically and mentally more fit.”

Dr. Luskin added that the study reports on outcomes through 2020, including years when newer regimens were not broadly disseminated outside of clinical trials.

Moving forward, she said, “this report suggests we need to continue to develop novel approaches and understand long-term outcomes as well as ‘real world’ outcomes. A similar study should be repeated again in 3-5 years as novel regimens become standard. We hope to see improvements.”

No study funding was reported. Dr. Koprivnikar disclosed consulting relationships with Alexion, GSK, Novartis, and Apellis. Other authors reported no disclosures. Dr. Luskin disclosed ties with Pfizer, Novartis, Jazz, Kite, and AbbVie.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

SAN DIEGO — Two proposed new multiple myeloma staging systems offer similar prognostic accuracy compared with the standard staging system, but the new systems provide more refined risk classifications across different disease stages. 

The findings should encourage greater use of these newer staging systems in routine clinical practice, first author Manni Mohyuddin, MD, said during a presentation at the American Society of Hematology annual meeting.

Dr. Mohyuddin and his colleagues retrospectively compared the standard Revised International Staging System (R-ISS) with two newer systems, the Second Revision of the R-ISS (R2-ISS) and the Mayo Additive Staging System (MASS), using real-world data from nearly 500 patients with newly diagnosed multiple myeloma.

The R-ISS, the most common multiple myeloma staging system, incorporates a range of prognostic features, including high-risk genetic markers assessed using fluorescence in situ hybridization as well as levels of lactate dehydrogenase, albumin, and beta-2 microglobulin, explained Dr. Mohyuddin, assistant professor at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

R2-ISS and MASS include additional factors that reflect experts’ growing understanding of multiple myeloma. Specifically, the systems also evaluate a gain of chromosome 1q, in which patients have an extra copy of chromosome 1q, as well as the additive effects of multiple high-risk cytogenetic abnormalities, both of which indicate worse prognosis in multiple myeloma, Dr. Mohyuddin said in an interview.

To compare the three staging systems, the investigators used information on newly diagnosed patients in the Flatiron Health EHR–derived deidentified database, which includes data from cancer clinics across the United States. Patients were followed from first-line treatment initiation until death, the end of the study period, or last recorded activity.

The patients from the database had a median age of 70 years, and most had not received a transplant. The most common cytogenetic abnormality was gain 1q, present in about one third of patients. 

Given that the R2-ISS originated from patients in clinical trials, Dr. Mohyuddin noted the importance of assessing how the system would perform in a real-world setting. 

Of the 497 patients in the analysis, the R-ISS staging system classified 24% as stage I, 63% as stage II, and 13% as stage III. Overall survival differed across these R-ISS stages, indicating the system was prognostic for survival. Median overall survival was not reached for those with stage I disease, was 62.9 months for those with stage II disease, and 37.6 months for those with stage III disease.

Because the R-ISS doesn’t consider the additive effect of multiple cytogenetic abnormalities, many patients end up in the R-ISS stage II category but ultimately may have vastly different outcomes, Dr. Mohyuddin said.

The R2-ISS includes four risk categories, which provide more granularity to the stage II classification: Stage I is low risk, stage II is low-intermediate, stage III is intermediate, and stage IV is high risk. Using this staging system, 20% of patients were stage I, 25% were stage II, 46% were stage III, and 9% were stage IV.

The R2-ISS was also prognostic for survival, which generally worsened from stage I to stage IV: Median overall survival was not reached in stage I patients, was 69.3 months for stage II, 50.0 months for stage III, and 50.6 months for stage IV patients. However, Dr. Mohyuddin noted that there was some overlap in the survival curves for stages I and II and for stages III and IV.

When applying MASS, 34% of patients were categorized as stage I, 35% as stage II, and 31% as stage III disease. This system was prognostic for survival as well, with median overall survival of 76.9 months for stage I, 61.2 months for stage II, and 45.0 months for stage III.

With R2-ISS, many of those in R-ISS stage II are moved into stage I and III. With MASS, the R-ISS stage II patients are more evenly distributed across stages I, II, and III.

In other words, “we show that both these newer staging systems basically recategorize patients into different stages,” essentially “decreasing the number of people in the large, ambiguous (R-ISS) stage II category,” said Dr. Mohyuddin. 

Dr. Mohyuddin and colleagues also evaluated the staging systems in fully adjusted analyses that controlled for age, race/ethnicity, sex, practice type, and diagnosis year. 

Using R2-ISS, stage I patients had a similar risk for death compared with stage II patients (hazard ratio [HR], 1.2). Compared with stage I patients, stage III and IV patients had comparable risks for death, both about 2.5-fold higher than in those with stage I disease (HR, 2.4 and 2.6, respectively). 

Compared with stage I MASS patients, those with stage II had a twofold higher risk for death (HR, 2.0), and those with stage III had an almost threefold higher risk (HR, 2.7). 

Although no system considers all factors associated with myeloma outcomes, R2-ISS and MASS do offer a benefit over R-ISS, Dr. Mohyuddin said.

He added that the R2-ISS and MASS are similar from a statistical standpoint, but he gave MASS a slight edge for use in clinical practice.

MASS “more cleanly demarcated [patients] into prognostic subsets,” plus it is “a little easier to remember by heart,” he explained. MASS also puts more emphasis on the presence of multiple high-risk cytogenetic abnormalities, which is a worse prognostic in this era of quadruplet therapy for multiple myeloma, he added.

Because the study largely took place in an era when triplet therapy dominated, “we would be curious to see, with longer follow-up and more use of quadruplets, how these staging systems would perform,” he said. 

Despite the benefits of these newer staging systems, many factors play a role in multiple myeloma outcomes, Dr. Mohyuddin explained. Staging systems are “only a piece of the puzzle.”

Dr. Mohyuddin reported having no financial interests to disclose.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Two proposed new multiple myeloma staging systems offer similar prognostic accuracy compared with the standard staging system, but the new systems provide more refined risk classifications across different disease stages. 

The findings should encourage greater use of these newer staging systems in routine clinical practice, first author Manni Mohyuddin, MD, said during a presentation at the American Society of Hematology annual meeting.

Dr. Mohyuddin and his colleagues retrospectively compared the standard Revised International Staging System (R-ISS) with two newer systems, the Second Revision of the R-ISS (R2-ISS) and the Mayo Additive Staging System (MASS), using real-world data from nearly 500 patients with newly diagnosed multiple myeloma.

The R-ISS, the most common multiple myeloma staging system, incorporates a range of prognostic features, including high-risk genetic markers assessed using fluorescence in situ hybridization as well as levels of lactate dehydrogenase, albumin, and beta-2 microglobulin, explained Dr. Mohyuddin, assistant professor at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

R2-ISS and MASS include additional factors that reflect experts’ growing understanding of multiple myeloma. Specifically, the systems also evaluate a gain of chromosome 1q, in which patients have an extra copy of chromosome 1q, as well as the additive effects of multiple high-risk cytogenetic abnormalities, both of which indicate worse prognosis in multiple myeloma, Dr. Mohyuddin said in an interview.

To compare the three staging systems, the investigators used information on newly diagnosed patients in the Flatiron Health EHR–derived deidentified database, which includes data from cancer clinics across the United States. Patients were followed from first-line treatment initiation until death, the end of the study period, or last recorded activity.

The patients from the database had a median age of 70 years, and most had not received a transplant. The most common cytogenetic abnormality was gain 1q, present in about one third of patients. 

Given that the R2-ISS originated from patients in clinical trials, Dr. Mohyuddin noted the importance of assessing how the system would perform in a real-world setting. 

Of the 497 patients in the analysis, the R-ISS staging system classified 24% as stage I, 63% as stage II, and 13% as stage III. Overall survival differed across these R-ISS stages, indicating the system was prognostic for survival. Median overall survival was not reached for those with stage I disease, was 62.9 months for those with stage II disease, and 37.6 months for those with stage III disease.

Because the R-ISS doesn’t consider the additive effect of multiple cytogenetic abnormalities, many patients end up in the R-ISS stage II category but ultimately may have vastly different outcomes, Dr. Mohyuddin said.

The R2-ISS includes four risk categories, which provide more granularity to the stage II classification: Stage I is low risk, stage II is low-intermediate, stage III is intermediate, and stage IV is high risk. Using this staging system, 20% of patients were stage I, 25% were stage II, 46% were stage III, and 9% were stage IV.

The R2-ISS was also prognostic for survival, which generally worsened from stage I to stage IV: Median overall survival was not reached in stage I patients, was 69.3 months for stage II, 50.0 months for stage III, and 50.6 months for stage IV patients. However, Dr. Mohyuddin noted that there was some overlap in the survival curves for stages I and II and for stages III and IV.

When applying MASS, 34% of patients were categorized as stage I, 35% as stage II, and 31% as stage III disease. This system was prognostic for survival as well, with median overall survival of 76.9 months for stage I, 61.2 months for stage II, and 45.0 months for stage III.

With R2-ISS, many of those in R-ISS stage II are moved into stage I and III. With MASS, the R-ISS stage II patients are more evenly distributed across stages I, II, and III.

In other words, “we show that both these newer staging systems basically recategorize patients into different stages,” essentially “decreasing the number of people in the large, ambiguous (R-ISS) stage II category,” said Dr. Mohyuddin. 

Dr. Mohyuddin and colleagues also evaluated the staging systems in fully adjusted analyses that controlled for age, race/ethnicity, sex, practice type, and diagnosis year. 

Using R2-ISS, stage I patients had a similar risk for death compared with stage II patients (hazard ratio [HR], 1.2). Compared with stage I patients, stage III and IV patients had comparable risks for death, both about 2.5-fold higher than in those with stage I disease (HR, 2.4 and 2.6, respectively). 

Compared with stage I MASS patients, those with stage II had a twofold higher risk for death (HR, 2.0), and those with stage III had an almost threefold higher risk (HR, 2.7). 

Although no system considers all factors associated with myeloma outcomes, R2-ISS and MASS do offer a benefit over R-ISS, Dr. Mohyuddin said.

He added that the R2-ISS and MASS are similar from a statistical standpoint, but he gave MASS a slight edge for use in clinical practice.

MASS “more cleanly demarcated [patients] into prognostic subsets,” plus it is “a little easier to remember by heart,” he explained. MASS also puts more emphasis on the presence of multiple high-risk cytogenetic abnormalities, which is a worse prognostic in this era of quadruplet therapy for multiple myeloma, he added.

Because the study largely took place in an era when triplet therapy dominated, “we would be curious to see, with longer follow-up and more use of quadruplets, how these staging systems would perform,” he said. 

Despite the benefits of these newer staging systems, many factors play a role in multiple myeloma outcomes, Dr. Mohyuddin explained. Staging systems are “only a piece of the puzzle.”

Dr. Mohyuddin reported having no financial interests to disclose.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Two proposed new multiple myeloma staging systems offer similar prognostic accuracy compared with the standard staging system, but the new systems provide more refined risk classifications across different disease stages. 

The findings should encourage greater use of these newer staging systems in routine clinical practice, first author Manni Mohyuddin, MD, said during a presentation at the American Society of Hematology annual meeting.

Dr. Mohyuddin and his colleagues retrospectively compared the standard Revised International Staging System (R-ISS) with two newer systems, the Second Revision of the R-ISS (R2-ISS) and the Mayo Additive Staging System (MASS), using real-world data from nearly 500 patients with newly diagnosed multiple myeloma.

The R-ISS, the most common multiple myeloma staging system, incorporates a range of prognostic features, including high-risk genetic markers assessed using fluorescence in situ hybridization as well as levels of lactate dehydrogenase, albumin, and beta-2 microglobulin, explained Dr. Mohyuddin, assistant professor at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

R2-ISS and MASS include additional factors that reflect experts’ growing understanding of multiple myeloma. Specifically, the systems also evaluate a gain of chromosome 1q, in which patients have an extra copy of chromosome 1q, as well as the additive effects of multiple high-risk cytogenetic abnormalities, both of which indicate worse prognosis in multiple myeloma, Dr. Mohyuddin said in an interview.

To compare the three staging systems, the investigators used information on newly diagnosed patients in the Flatiron Health EHR–derived deidentified database, which includes data from cancer clinics across the United States. Patients were followed from first-line treatment initiation until death, the end of the study period, or last recorded activity.

The patients from the database had a median age of 70 years, and most had not received a transplant. The most common cytogenetic abnormality was gain 1q, present in about one third of patients. 

Given that the R2-ISS originated from patients in clinical trials, Dr. Mohyuddin noted the importance of assessing how the system would perform in a real-world setting. 

Of the 497 patients in the analysis, the R-ISS staging system classified 24% as stage I, 63% as stage II, and 13% as stage III. Overall survival differed across these R-ISS stages, indicating the system was prognostic for survival. Median overall survival was not reached for those with stage I disease, was 62.9 months for those with stage II disease, and 37.6 months for those with stage III disease.

Because the R-ISS doesn’t consider the additive effect of multiple cytogenetic abnormalities, many patients end up in the R-ISS stage II category but ultimately may have vastly different outcomes, Dr. Mohyuddin said.

The R2-ISS includes four risk categories, which provide more granularity to the stage II classification: Stage I is low risk, stage II is low-intermediate, stage III is intermediate, and stage IV is high risk. Using this staging system, 20% of patients were stage I, 25% were stage II, 46% were stage III, and 9% were stage IV.

The R2-ISS was also prognostic for survival, which generally worsened from stage I to stage IV: Median overall survival was not reached in stage I patients, was 69.3 months for stage II, 50.0 months for stage III, and 50.6 months for stage IV patients. However, Dr. Mohyuddin noted that there was some overlap in the survival curves for stages I and II and for stages III and IV.

When applying MASS, 34% of patients were categorized as stage I, 35% as stage II, and 31% as stage III disease. This system was prognostic for survival as well, with median overall survival of 76.9 months for stage I, 61.2 months for stage II, and 45.0 months for stage III.

With R2-ISS, many of those in R-ISS stage II are moved into stage I and III. With MASS, the R-ISS stage II patients are more evenly distributed across stages I, II, and III.

In other words, “we show that both these newer staging systems basically recategorize patients into different stages,” essentially “decreasing the number of people in the large, ambiguous (R-ISS) stage II category,” said Dr. Mohyuddin. 

Dr. Mohyuddin and colleagues also evaluated the staging systems in fully adjusted analyses that controlled for age, race/ethnicity, sex, practice type, and diagnosis year. 

Using R2-ISS, stage I patients had a similar risk for death compared with stage II patients (hazard ratio [HR], 1.2). Compared with stage I patients, stage III and IV patients had comparable risks for death, both about 2.5-fold higher than in those with stage I disease (HR, 2.4 and 2.6, respectively). 

Compared with stage I MASS patients, those with stage II had a twofold higher risk for death (HR, 2.0), and those with stage III had an almost threefold higher risk (HR, 2.7). 

Although no system considers all factors associated with myeloma outcomes, R2-ISS and MASS do offer a benefit over R-ISS, Dr. Mohyuddin said.

He added that the R2-ISS and MASS are similar from a statistical standpoint, but he gave MASS a slight edge for use in clinical practice.

MASS “more cleanly demarcated [patients] into prognostic subsets,” plus it is “a little easier to remember by heart,” he explained. MASS also puts more emphasis on the presence of multiple high-risk cytogenetic abnormalities, which is a worse prognostic in this era of quadruplet therapy for multiple myeloma, he added.

Because the study largely took place in an era when triplet therapy dominated, “we would be curious to see, with longer follow-up and more use of quadruplets, how these staging systems would perform,” he said. 

Despite the benefits of these newer staging systems, many factors play a role in multiple myeloma outcomes, Dr. Mohyuddin explained. Staging systems are “only a piece of the puzzle.”

Dr. Mohyuddin reported having no financial interests to disclose.
 

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as “preferred” regimens, according to National Comprehensive Cancer Network guidelines. However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.

The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.

In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the annual meeting of the American Society of Hematology.

Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.

For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.

To more directly compare the efficacy of the two regimens, Dr. Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts. 

After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis. 

During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died. 

The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).

Dr. Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.

The outcome measure combined time-to-next treatment and time to death; however, Dr. Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.

Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Dr. Hansen concluded. 

The study was supported by Janssen. Dr. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Long-term follow-up from the only randomized controlled trial to compare salvage autologous stem cell transplant with a standard two-drug regimen in patients with relapsed or refractory multiple myeloma found no benefit to salvage transplant. 

Patients receiving a second, salvage-autologous stem cell transplant alongside lenalidomide-dexamethasone maintenance therapy did not demonstrate improved progression-free survival (PFS) or overall survival compared with patients who continued the two-drug regimen without salvage transplant, according to research presented at the American Society of Hematology annual meeting.

The primary phase 3 analysis, published in 2021, showed no survival benefit following salvage transplant at the time of relapse, though it only followed patients for a median of 37 months. 

However, because a significant fraction of patients in the transplant arm — about 29% — did not undergo the planned salvage transplant before dropping out of the study, the researchers performed further analyses that “suggested a survival benefit in patients who actually received the transplant,” first author Marc-Andrea Baertsch, MD, of the German Cancer Research Center and University Hospital Heidelberg, reported at ASH.

Now, the latest analysis, which followed patients for a median of 99 months (8.25 years), confirmed the initial 2021 findings, Dr. Baertsch explained. 

“The writing on the wall is clear: Don’t repeat a transplant at the time of relapse for those who have already gotten a transplant,” said Manni Mohyuddin, MD, of the University of Utah in Salt Lake City, who was not involved in the research. Dr. Mohyuddin added, however, that this finding doesn’t apply to those who haven’t yet gotten a transplant. “Data from other trials suggests a role of transplant in this situation, depending on the unique circumstances.” 

The current trial included 282 adult patients, aged 75 years or younger, with relapsed or refractory multiple myeloma. Between 2010 and 2016, patients in the intention-to-treat analysis (n = 277) were randomized to lenalidomide-dexamethasone reinduction and maintenance, along with salvage high-dose chemotherapy with melphalan and autologous stem cell transplantation (n = 139) or just continuous lenalidomide-dexamethasone until progression (n = 138). 

Patients in both arms received three cycles of lenalidomide-dexamethasone up front: 25 mg of lenalidomide on days 1 through 21, and 40 mg of dexamethasone on days 1, 8, 15, and 22 in 4-week cycles. Those in the salvage transplant arm then received high-dose chemotherapy with 200 mg/m² of melphalan followed by transplant and 10 mg of lenalidomide maintenance therapy daily, while those in the control arm continued with receiving lenalidomide-dexamethasone.

All patients had received one to three prior lines of therapy, had good performance status, and had a time-to-disease-progression of at least 12 months after frontline autologous stem cell transplant.

In the primary 2021 study, patients in the salvage transplant group did not demonstrate a survival benefit (hazard ratio [HR] for PFS, 0.87; HR for overall survival, 0.81). 

In the latest analysis, no survival benefit emerged after following patients for a median of about 8 years. Patients in the salvage transplant arm had a median PFS of 20.5 months vs 19.3 months in the continuous therapy arms (HR, 0.98; 95% CI, 0.76-1.27; P = .9). Median overall survival was 67.1 months in the salvage transplant arm and 62.7 months in the continuous treatment arm (HR, 0.89; 95% CI, 0.66 - 1.20; P = .44).

Time to first progression after frontline transplant was associated with a PFS benefit but did not predict an overall survival benefit, Dr. Baertsch noted. 

When evaluating outcomes from the time of salvage transplant to account for the high number of dropouts, the PFS and overall survival findings held. Patients who received salvage transplant did not experience significantly improved PFS (HR, 0.91) or overall survival (76.3 months in the salvage group vs 65.9 months in the continuous treatment arm; HR, 0.80). 

The lack of PFS and overall survival benefit occurred across all myeloma subgroups, Dr. Baertsch said. 

Overall, the results indicate that “ a repeat transplant at the time of relapse for patients who had already gotten a transplant previously was no better than continuing a two-drug regimen,” Dr. Mohyuddin said.

However, he noted, “a lot has changed for myeloma care” since this trial was initially conducted. “We now have better regimens available that do not involve a transplant. If a repeat transplant couldn’t beat a two-drug regimen, it surely cannot beat a three drug or four drug regimen.” 

Dr. Baertsch reported no disclosures.

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

SAN DIEGO — Long-term follow-up from the only randomized controlled trial to compare salvage autologous stem cell transplant with a standard two-drug regimen in patients with relapsed or refractory multiple myeloma found no benefit to salvage transplant. 

Patients receiving a second, salvage-autologous stem cell transplant alongside lenalidomide-dexamethasone maintenance therapy did not demonstrate improved progression-free survival (PFS) or overall survival compared with patients who continued the two-drug regimen without salvage transplant, according to research presented at the American Society of Hematology annual meeting.

The primary phase 3 analysis, published in 2021, showed no survival benefit following salvage transplant at the time of relapse, though it only followed patients for a median of 37 months. 

However, because a significant fraction of patients in the transplant arm — about 29% — did not undergo the planned salvage transplant before dropping out of the study, the researchers performed further analyses that “suggested a survival benefit in patients who actually received the transplant,” first author Marc-Andrea Baertsch, MD, of the German Cancer Research Center and University Hospital Heidelberg, reported at ASH.

Now, the latest analysis, which followed patients for a median of 99 months (8.25 years), confirmed the initial 2021 findings, Dr. Baertsch explained. 

“The writing on the wall is clear: Don’t repeat a transplant at the time of relapse for those who have already gotten a transplant,” said Manni Mohyuddin, MD, of the University of Utah in Salt Lake City, who was not involved in the research. Dr. Mohyuddin added, however, that this finding doesn’t apply to those who haven’t yet gotten a transplant. “Data from other trials suggests a role of transplant in this situation, depending on the unique circumstances.” 

The current trial included 282 adult patients, aged 75 years or younger, with relapsed or refractory multiple myeloma. Between 2010 and 2016, patients in the intention-to-treat analysis (n = 277) were randomized to lenalidomide-dexamethasone reinduction and maintenance, along with salvage high-dose chemotherapy with melphalan and autologous stem cell transplantation (n = 139) or just continuous lenalidomide-dexamethasone until progression (n = 138). 

Patients in both arms received three cycles of lenalidomide-dexamethasone up front: 25 mg of lenalidomide on days 1 through 21, and 40 mg of dexamethasone on days 1, 8, 15, and 22 in 4-week cycles. Those in the salvage transplant arm then received high-dose chemotherapy with 200 mg/m² of melphalan followed by transplant and 10 mg of lenalidomide maintenance therapy daily, while those in the control arm continued with receiving lenalidomide-dexamethasone.

All patients had received one to three prior lines of therapy, had good performance status, and had a time-to-disease-progression of at least 12 months after frontline autologous stem cell transplant.

In the primary 2021 study, patients in the salvage transplant group did not demonstrate a survival benefit (hazard ratio [HR] for PFS, 0.87; HR for overall survival, 0.81). 

In the latest analysis, no survival benefit emerged after following patients for a median of about 8 years. Patients in the salvage transplant arm had a median PFS of 20.5 months vs 19.3 months in the continuous therapy arms (HR, 0.98; 95% CI, 0.76-1.27; P = .9). Median overall survival was 67.1 months in the salvage transplant arm and 62.7 months in the continuous treatment arm (HR, 0.89; 95% CI, 0.66 - 1.20; P = .44).

Time to first progression after frontline transplant was associated with a PFS benefit but did not predict an overall survival benefit, Dr. Baertsch noted. 

When evaluating outcomes from the time of salvage transplant to account for the high number of dropouts, the PFS and overall survival findings held. Patients who received salvage transplant did not experience significantly improved PFS (HR, 0.91) or overall survival (76.3 months in the salvage group vs 65.9 months in the continuous treatment arm; HR, 0.80). 

The lack of PFS and overall survival benefit occurred across all myeloma subgroups, Dr. Baertsch said. 

Overall, the results indicate that “ a repeat transplant at the time of relapse for patients who had already gotten a transplant previously was no better than continuing a two-drug regimen,” Dr. Mohyuddin said.

However, he noted, “a lot has changed for myeloma care” since this trial was initially conducted. “We now have better regimens available that do not involve a transplant. If a repeat transplant couldn’t beat a two-drug regimen, it surely cannot beat a three drug or four drug regimen.” 

Dr. Baertsch reported no disclosures.

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

SAN DIEGO — Long-term follow-up from the only randomized controlled trial to compare salvage autologous stem cell transplant with a standard two-drug regimen in patients with relapsed or refractory multiple myeloma found no benefit to salvage transplant. 

Patients receiving a second, salvage-autologous stem cell transplant alongside lenalidomide-dexamethasone maintenance therapy did not demonstrate improved progression-free survival (PFS) or overall survival compared with patients who continued the two-drug regimen without salvage transplant, according to research presented at the American Society of Hematology annual meeting.

The primary phase 3 analysis, published in 2021, showed no survival benefit following salvage transplant at the time of relapse, though it only followed patients for a median of 37 months. 

However, because a significant fraction of patients in the transplant arm — about 29% — did not undergo the planned salvage transplant before dropping out of the study, the researchers performed further analyses that “suggested a survival benefit in patients who actually received the transplant,” first author Marc-Andrea Baertsch, MD, of the German Cancer Research Center and University Hospital Heidelberg, reported at ASH.

Now, the latest analysis, which followed patients for a median of 99 months (8.25 years), confirmed the initial 2021 findings, Dr. Baertsch explained. 

“The writing on the wall is clear: Don’t repeat a transplant at the time of relapse for those who have already gotten a transplant,” said Manni Mohyuddin, MD, of the University of Utah in Salt Lake City, who was not involved in the research. Dr. Mohyuddin added, however, that this finding doesn’t apply to those who haven’t yet gotten a transplant. “Data from other trials suggests a role of transplant in this situation, depending on the unique circumstances.” 

The current trial included 282 adult patients, aged 75 years or younger, with relapsed or refractory multiple myeloma. Between 2010 and 2016, patients in the intention-to-treat analysis (n = 277) were randomized to lenalidomide-dexamethasone reinduction and maintenance, along with salvage high-dose chemotherapy with melphalan and autologous stem cell transplantation (n = 139) or just continuous lenalidomide-dexamethasone until progression (n = 138). 

Patients in both arms received three cycles of lenalidomide-dexamethasone up front: 25 mg of lenalidomide on days 1 through 21, and 40 mg of dexamethasone on days 1, 8, 15, and 22 in 4-week cycles. Those in the salvage transplant arm then received high-dose chemotherapy with 200 mg/m² of melphalan followed by transplant and 10 mg of lenalidomide maintenance therapy daily, while those in the control arm continued with receiving lenalidomide-dexamethasone.

All patients had received one to three prior lines of therapy, had good performance status, and had a time-to-disease-progression of at least 12 months after frontline autologous stem cell transplant.

In the primary 2021 study, patients in the salvage transplant group did not demonstrate a survival benefit (hazard ratio [HR] for PFS, 0.87; HR for overall survival, 0.81). 

In the latest analysis, no survival benefit emerged after following patients for a median of about 8 years. Patients in the salvage transplant arm had a median PFS of 20.5 months vs 19.3 months in the continuous therapy arms (HR, 0.98; 95% CI, 0.76-1.27; P = .9). Median overall survival was 67.1 months in the salvage transplant arm and 62.7 months in the continuous treatment arm (HR, 0.89; 95% CI, 0.66 - 1.20; P = .44).

Time to first progression after frontline transplant was associated with a PFS benefit but did not predict an overall survival benefit, Dr. Baertsch noted. 

When evaluating outcomes from the time of salvage transplant to account for the high number of dropouts, the PFS and overall survival findings held. Patients who received salvage transplant did not experience significantly improved PFS (HR, 0.91) or overall survival (76.3 months in the salvage group vs 65.9 months in the continuous treatment arm; HR, 0.80). 

The lack of PFS and overall survival benefit occurred across all myeloma subgroups, Dr. Baertsch said. 

Overall, the results indicate that “ a repeat transplant at the time of relapse for patients who had already gotten a transplant previously was no better than continuing a two-drug regimen,” Dr. Mohyuddin said.

However, he noted, “a lot has changed for myeloma care” since this trial was initially conducted. “We now have better regimens available that do not involve a transplant. If a repeat transplant couldn’t beat a two-drug regimen, it surely cannot beat a three drug or four drug regimen.” 

Dr. Baertsch reported no disclosures.

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

SAN DIEGO — The average age of death for Black U.S. patients with sickle cell disease (SCD) rose from 39 years (females = 40, males = 38) in 1999-2009 to 43 years (females = 44, males = 41) in 2010-2020, reflecting improvements in treatment, a new study finds.

But the news is not all positive. Mortality rates still jumped markedly as patients transitioned from pediatric to adult care, lead author Kristine A. Karkoska, MD, a pediatric hematology/oncologist with the University of Cincinnati College of Medicine, said at the annual meeting of the American Society of Hematology.

“This reflects that young adults are getting lost to care, and then they’re presenting with acute, life-threatening complications,” she said. “We still need more emphasis on comprehensive lifetime sickle-cell care and the transition to adult clinics to improve mortality in young adults.”

According to Dr. Karkoska, researchers launched the analysis of sickle-cell mortality rates to update previously available data up to the year 2009, which showed improvements as current standard-of-care treatments were introduced. Updated numbers, she said, would reflect the influence of a rise in dedicated SCD clinics and a 2014 National Heart, Lung, and Blood Institute recommendation that all children with SCD be treated with hydroxyurea starting at 9 months.

For the study, Dr. Karkoska and colleagues analyzed mortality statistics from the period of 1979-2020 via a CDC database. They found that 5272 Black patients died of SCD from 2010 to 2020. The crude mortality rate was 1.1 per 100,000 Black people, lower than the 1.2 per 100,000 rate of 1999-2009 (P < .0001).

The researchers also found that from 2010 to 2020, the mortality rate jumped for patients in the 15-19 to 20-24 age group: It rose from 0.9 per 100,000 to 1.4 per 100,000, P < .0001).

The researchers also examined contributors to death other than SCD. In 39% of cases, underlying causes were noted: cardiovascular disease (28%), accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The population of people with SCD is “getting older, and they’re developing a combination of both sickle-related chronic organ damage as well as non-sickle-related chronic disease,” Dr. Karkoska said.

She noted that limitations include a reliance on data that can be incomplete or inaccurate. She also mentioned that the study only focuses on Black patients, who make up the vast majority of those with SCD.

How good is the news about improved mortality numbers? One member of the audience at the ASH presentation was disappointed that they hadn’t gotten even better. “I was hoping to come here to be cheered up,” he said, “and I’m not.”

Three physicians who didn’t take part in the research but are familiar with the new study spoke in interviews about the findings.

Michael Bender, MD, PhD, director of the Odessa Brown Comprehensive Sickle Cell Clinic in Seattle, pointed out that mortality rates improve slowly over time, as new treatments enter the picture. When new therapies come along, he said, “it’s tough if someone’s already 40 years old and their body has gone through a lot. They’re not going to have as much benefit as someone who started [on therapy] when they were 5 years old, and they grew up with that improvement.”

Sickle cell specialist Asmaa Ferdjallah, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, said that the data showing a spike in mortality rates during the pediatric-adult transition are not surprising but still “really hard to digest.”

“It is a testament to the fact that we are not meeting patients where they are,” she said. “We struggle immensely with the transition period. This is something that is difficult across all providers all over the country,” she said. “There are different ways to ensure a successful transition from the pediatric side to the adult side. Here at Mayo Clinic, we use a slow transition, and we rotate appointments with peds and adults until age 30.”

Sophie Miriam Lanzkron, MD, MHS, director of the Sickle Cell Center for Adults at Johns Hopkins Hospital, Baltimore, said increases in mortality in the post-pediatric period appear to be due in part to “lack of access to high-quality sickle cell care for adults because there aren’t enough hematologists.” Worsening disease due to aging is another factor, she said, and “there might also be some behavioral changes. Young people think they will live forever. Sometimes they choose not to adhere to medical recommendations, which for this population is very risky.”

Dr. Lanzkron said her team is developing a long-term patient registry that should provide more insight.

No study funding was reported. Dr. Karkoska had no disclosures. The other coauthor disclosed research funding and safety advisory board relationships with Novartis. Dr. Ferdjallah, Dr. Lanzkron, and Dr. Bender reported no disclosures.

SAN DIEGO — The average age of death for Black U.S. patients with sickle cell disease (SCD) rose from 39 years (females = 40, males = 38) in 1999-2009 to 43 years (females = 44, males = 41) in 2010-2020, reflecting improvements in treatment, a new study finds.

But the news is not all positive. Mortality rates still jumped markedly as patients transitioned from pediatric to adult care, lead author Kristine A. Karkoska, MD, a pediatric hematology/oncologist with the University of Cincinnati College of Medicine, said at the annual meeting of the American Society of Hematology.

“This reflects that young adults are getting lost to care, and then they’re presenting with acute, life-threatening complications,” she said. “We still need more emphasis on comprehensive lifetime sickle-cell care and the transition to adult clinics to improve mortality in young adults.”

According to Dr. Karkoska, researchers launched the analysis of sickle-cell mortality rates to update previously available data up to the year 2009, which showed improvements as current standard-of-care treatments were introduced. Updated numbers, she said, would reflect the influence of a rise in dedicated SCD clinics and a 2014 National Heart, Lung, and Blood Institute recommendation that all children with SCD be treated with hydroxyurea starting at 9 months.

For the study, Dr. Karkoska and colleagues analyzed mortality statistics from the period of 1979-2020 via a CDC database. They found that 5272 Black patients died of SCD from 2010 to 2020. The crude mortality rate was 1.1 per 100,000 Black people, lower than the 1.2 per 100,000 rate of 1999-2009 (P < .0001).

The researchers also found that from 2010 to 2020, the mortality rate jumped for patients in the 15-19 to 20-24 age group: It rose from 0.9 per 100,000 to 1.4 per 100,000, P < .0001).

The researchers also examined contributors to death other than SCD. In 39% of cases, underlying causes were noted: cardiovascular disease (28%), accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The population of people with SCD is “getting older, and they’re developing a combination of both sickle-related chronic organ damage as well as non-sickle-related chronic disease,” Dr. Karkoska said.

She noted that limitations include a reliance on data that can be incomplete or inaccurate. She also mentioned that the study only focuses on Black patients, who make up the vast majority of those with SCD.

How good is the news about improved mortality numbers? One member of the audience at the ASH presentation was disappointed that they hadn’t gotten even better. “I was hoping to come here to be cheered up,” he said, “and I’m not.”

Three physicians who didn’t take part in the research but are familiar with the new study spoke in interviews about the findings.

Michael Bender, MD, PhD, director of the Odessa Brown Comprehensive Sickle Cell Clinic in Seattle, pointed out that mortality rates improve slowly over time, as new treatments enter the picture. When new therapies come along, he said, “it’s tough if someone’s already 40 years old and their body has gone through a lot. They’re not going to have as much benefit as someone who started [on therapy] when they were 5 years old, and they grew up with that improvement.”

Sickle cell specialist Asmaa Ferdjallah, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, said that the data showing a spike in mortality rates during the pediatric-adult transition are not surprising but still “really hard to digest.”

“It is a testament to the fact that we are not meeting patients where they are,” she said. “We struggle immensely with the transition period. This is something that is difficult across all providers all over the country,” she said. “There are different ways to ensure a successful transition from the pediatric side to the adult side. Here at Mayo Clinic, we use a slow transition, and we rotate appointments with peds and adults until age 30.”

Sophie Miriam Lanzkron, MD, MHS, director of the Sickle Cell Center for Adults at Johns Hopkins Hospital, Baltimore, said increases in mortality in the post-pediatric period appear to be due in part to “lack of access to high-quality sickle cell care for adults because there aren’t enough hematologists.” Worsening disease due to aging is another factor, she said, and “there might also be some behavioral changes. Young people think they will live forever. Sometimes they choose not to adhere to medical recommendations, which for this population is very risky.”

Dr. Lanzkron said her team is developing a long-term patient registry that should provide more insight.

No study funding was reported. Dr. Karkoska had no disclosures. The other coauthor disclosed research funding and safety advisory board relationships with Novartis. Dr. Ferdjallah, Dr. Lanzkron, and Dr. Bender reported no disclosures.

SAN DIEGO — The average age of death for Black U.S. patients with sickle cell disease (SCD) rose from 39 years (females = 40, males = 38) in 1999-2009 to 43 years (females = 44, males = 41) in 2010-2020, reflecting improvements in treatment, a new study finds.

But the news is not all positive. Mortality rates still jumped markedly as patients transitioned from pediatric to adult care, lead author Kristine A. Karkoska, MD, a pediatric hematology/oncologist with the University of Cincinnati College of Medicine, said at the annual meeting of the American Society of Hematology.

“This reflects that young adults are getting lost to care, and then they’re presenting with acute, life-threatening complications,” she said. “We still need more emphasis on comprehensive lifetime sickle-cell care and the transition to adult clinics to improve mortality in young adults.”

According to Dr. Karkoska, researchers launched the analysis of sickle-cell mortality rates to update previously available data up to the year 2009, which showed improvements as current standard-of-care treatments were introduced. Updated numbers, she said, would reflect the influence of a rise in dedicated SCD clinics and a 2014 National Heart, Lung, and Blood Institute recommendation that all children with SCD be treated with hydroxyurea starting at 9 months.

For the study, Dr. Karkoska and colleagues analyzed mortality statistics from the period of 1979-2020 via a CDC database. They found that 5272 Black patients died of SCD from 2010 to 2020. The crude mortality rate was 1.1 per 100,000 Black people, lower than the 1.2 per 100,000 rate of 1999-2009 (P < .0001).

The researchers also found that from 2010 to 2020, the mortality rate jumped for patients in the 15-19 to 20-24 age group: It rose from 0.9 per 100,000 to 1.4 per 100,000, P < .0001).

The researchers also examined contributors to death other than SCD. In 39% of cases, underlying causes were noted: cardiovascular disease (28%), accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The population of people with SCD is “getting older, and they’re developing a combination of both sickle-related chronic organ damage as well as non-sickle-related chronic disease,” Dr. Karkoska said.

She noted that limitations include a reliance on data that can be incomplete or inaccurate. She also mentioned that the study only focuses on Black patients, who make up the vast majority of those with SCD.

How good is the news about improved mortality numbers? One member of the audience at the ASH presentation was disappointed that they hadn’t gotten even better. “I was hoping to come here to be cheered up,” he said, “and I’m not.”

Three physicians who didn’t take part in the research but are familiar with the new study spoke in interviews about the findings.

Michael Bender, MD, PhD, director of the Odessa Brown Comprehensive Sickle Cell Clinic in Seattle, pointed out that mortality rates improve slowly over time, as new treatments enter the picture. When new therapies come along, he said, “it’s tough if someone’s already 40 years old and their body has gone through a lot. They’re not going to have as much benefit as someone who started [on therapy] when they were 5 years old, and they grew up with that improvement.”

Sickle cell specialist Asmaa Ferdjallah, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, said that the data showing a spike in mortality rates during the pediatric-adult transition are not surprising but still “really hard to digest.”

“It is a testament to the fact that we are not meeting patients where they are,” she said. “We struggle immensely with the transition period. This is something that is difficult across all providers all over the country,” she said. “There are different ways to ensure a successful transition from the pediatric side to the adult side. Here at Mayo Clinic, we use a slow transition, and we rotate appointments with peds and adults until age 30.”

Sophie Miriam Lanzkron, MD, MHS, director of the Sickle Cell Center for Adults at Johns Hopkins Hospital, Baltimore, said increases in mortality in the post-pediatric period appear to be due in part to “lack of access to high-quality sickle cell care for adults because there aren’t enough hematologists.” Worsening disease due to aging is another factor, she said, and “there might also be some behavioral changes. Young people think they will live forever. Sometimes they choose not to adhere to medical recommendations, which for this population is very risky.”

Dr. Lanzkron said her team is developing a long-term patient registry that should provide more insight.

No study funding was reported. Dr. Karkoska had no disclosures. The other coauthor disclosed research funding and safety advisory board relationships with Novartis. Dr. Ferdjallah, Dr. Lanzkron, and Dr. Bender reported no disclosures.

SAN DIEGO — Allogeneic stem cell transplant is associated with a significant survival benefit in patients with NPM1-mutated acute myeloid leukemia (AML) who are in their first complete remission and have measurable residual disease (MRD) after two courses of induction therapy, according to an analysis of UK National Cancer Research Institute study data.

This survival benefit did not extend to patients who were MRD-negative after their second induction therapy, Jad Othman, MBBS, reported at the American Society of Hematology annual meeting.

The findings confirm the value of assessing MRD after induction chemotherapy to help identify patients with NPM1-mutated AML in first complete remission who are more likely to benefit from allogeneic transplant, said Dr. Othman, of King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London, and the University of Sydney, Australia.

Recently, updated European LeukemiaNet recommendations, which stratify patients with AML by favorable, intermediate, and adverse prognoses, now include a revised genetic-risk classification. This classification generally considers NPM1-mutated AML favorable risk. However, having a co-mutation with FLT3-ITD raises the risk to intermediate.

Despite this increased granularity in risk stratification, “it’s still not really clear who should have transplant in first remission with NPM1-mutated AML,” Dr. Othman said. “And there is still significant variation in practice, not just worldwide but even center to center.” 

Although accumulating evidence suggests that MRD-negative patients with intermediate-risk AML are unlikely to benefit from allogeneic transplant in first complete remission, the presence of a FLT3-ITD mutation is often considered an indication for transplant, Othman explained. However, most studies supporting this view occurred before the development of sensitive molecular MRD measurement techniques.

The latest findings, from two sequential prospective randomized trials of intensive chemotherapy in adults aged 18-60 years with newly diagnosed AML may help clarify who will probably benefit from transplant and who won’t based on MRD status and relevant molecular features. 

The first study (AML17), conducted from 2009 to 2014, selected patients for transplant in first complete remission using a validated risk score that incorporated features including age, sex, and response after therapy. The other (AML19), conducted from 2015 to 2020, selected patients with NPM1-mutated AML for transplant only if they tested positive for MRD in peripheral blood after their second course of treatment, regardless of FLT3-ITD status or other baseline risk factors. 

Overall, the current analysis included the 737 patients with NPM1-mutated AML, 348 from AML17 and 389 from AML19, who were in complete remission after two courses of treatment and had an MRD sample at that point. 

In AML17, 27% of MRD-positive patients (16 of 60) and 18% of MRD-negative patients (52 of 288) underwent transplant in first complete remission compared with 60% (50 of 83) and 16% (49 of 306), respectively, in AML19. 

Among all 737 patients, Dr. Othman and colleagues did not observe an overall survival benefit among those who underwent transplant vs those who did not (hazard ratio [HR], 1.01) or among patients who were MRD-negative (HR, 0.82).

However, patients who were MRD-positive did have a significant survival advantage after transplant (HR, 0.39). In these patients, 3-year overall survival was 61% among those who underwent transplant vs 24% among those who did not. 

In MRD-negative patients, transplant in first complete remission did not improve overall survival despite improved relapse-free survival (HR, 0.50). This outcome, Othman explained, probably occurred because most patients who did not undergo transplant and who relapsed were salvaged, with about two thirds undergoing a transplant during their second complete response.

Results in patients with NPM1 FLT3-ITD co-mutation mirrored those in the overall population: MRD-positive patients in first complete remission who underwent transplant demonstrated improved overall survival compared with those without transplant (HR, 0.52), but the overall survival benefit did not extend to MRD-negative patients (HR, 0.80).

The findings show that molecular MRD after induction chemotherapy can identify patients with NPM1-mutated AML who are more likely to benefit from transplant in first remission, Dr. Othman concluded. However, he noted, because only 16% of patients overall were older than 60 years, the results may not be generalizable to older patients.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Allogeneic stem cell transplant is associated with a significant survival benefit in patients with NPM1-mutated acute myeloid leukemia (AML) who are in their first complete remission and have measurable residual disease (MRD) after two courses of induction therapy, according to an analysis of UK National Cancer Research Institute study data.

This survival benefit did not extend to patients who were MRD-negative after their second induction therapy, Jad Othman, MBBS, reported at the American Society of Hematology annual meeting.

The findings confirm the value of assessing MRD after induction chemotherapy to help identify patients with NPM1-mutated AML in first complete remission who are more likely to benefit from allogeneic transplant, said Dr. Othman, of King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London, and the University of Sydney, Australia.

Recently, updated European LeukemiaNet recommendations, which stratify patients with AML by favorable, intermediate, and adverse prognoses, now include a revised genetic-risk classification. This classification generally considers NPM1-mutated AML favorable risk. However, having a co-mutation with FLT3-ITD raises the risk to intermediate.

Despite this increased granularity in risk stratification, “it’s still not really clear who should have transplant in first remission with NPM1-mutated AML,” Dr. Othman said. “And there is still significant variation in practice, not just worldwide but even center to center.” 

Although accumulating evidence suggests that MRD-negative patients with intermediate-risk AML are unlikely to benefit from allogeneic transplant in first complete remission, the presence of a FLT3-ITD mutation is often considered an indication for transplant, Othman explained. However, most studies supporting this view occurred before the development of sensitive molecular MRD measurement techniques.

The latest findings, from two sequential prospective randomized trials of intensive chemotherapy in adults aged 18-60 years with newly diagnosed AML may help clarify who will probably benefit from transplant and who won’t based on MRD status and relevant molecular features. 

The first study (AML17), conducted from 2009 to 2014, selected patients for transplant in first complete remission using a validated risk score that incorporated features including age, sex, and response after therapy. The other (AML19), conducted from 2015 to 2020, selected patients with NPM1-mutated AML for transplant only if they tested positive for MRD in peripheral blood after their second course of treatment, regardless of FLT3-ITD status or other baseline risk factors. 

Overall, the current analysis included the 737 patients with NPM1-mutated AML, 348 from AML17 and 389 from AML19, who were in complete remission after two courses of treatment and had an MRD sample at that point. 

In AML17, 27% of MRD-positive patients (16 of 60) and 18% of MRD-negative patients (52 of 288) underwent transplant in first complete remission compared with 60% (50 of 83) and 16% (49 of 306), respectively, in AML19. 

Among all 737 patients, Dr. Othman and colleagues did not observe an overall survival benefit among those who underwent transplant vs those who did not (hazard ratio [HR], 1.01) or among patients who were MRD-negative (HR, 0.82).

However, patients who were MRD-positive did have a significant survival advantage after transplant (HR, 0.39). In these patients, 3-year overall survival was 61% among those who underwent transplant vs 24% among those who did not. 

In MRD-negative patients, transplant in first complete remission did not improve overall survival despite improved relapse-free survival (HR, 0.50). This outcome, Othman explained, probably occurred because most patients who did not undergo transplant and who relapsed were salvaged, with about two thirds undergoing a transplant during their second complete response.

Results in patients with NPM1 FLT3-ITD co-mutation mirrored those in the overall population: MRD-positive patients in first complete remission who underwent transplant demonstrated improved overall survival compared with those without transplant (HR, 0.52), but the overall survival benefit did not extend to MRD-negative patients (HR, 0.80).

The findings show that molecular MRD after induction chemotherapy can identify patients with NPM1-mutated AML who are more likely to benefit from transplant in first remission, Dr. Othman concluded. However, he noted, because only 16% of patients overall were older than 60 years, the results may not be generalizable to older patients.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Allogeneic stem cell transplant is associated with a significant survival benefit in patients with NPM1-mutated acute myeloid leukemia (AML) who are in their first complete remission and have measurable residual disease (MRD) after two courses of induction therapy, according to an analysis of UK National Cancer Research Institute study data.

This survival benefit did not extend to patients who were MRD-negative after their second induction therapy, Jad Othman, MBBS, reported at the American Society of Hematology annual meeting.

The findings confirm the value of assessing MRD after induction chemotherapy to help identify patients with NPM1-mutated AML in first complete remission who are more likely to benefit from allogeneic transplant, said Dr. Othman, of King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London, and the University of Sydney, Australia.

Recently, updated European LeukemiaNet recommendations, which stratify patients with AML by favorable, intermediate, and adverse prognoses, now include a revised genetic-risk classification. This classification generally considers NPM1-mutated AML favorable risk. However, having a co-mutation with FLT3-ITD raises the risk to intermediate.

Despite this increased granularity in risk stratification, “it’s still not really clear who should have transplant in first remission with NPM1-mutated AML,” Dr. Othman said. “And there is still significant variation in practice, not just worldwide but even center to center.” 

Although accumulating evidence suggests that MRD-negative patients with intermediate-risk AML are unlikely to benefit from allogeneic transplant in first complete remission, the presence of a FLT3-ITD mutation is often considered an indication for transplant, Othman explained. However, most studies supporting this view occurred before the development of sensitive molecular MRD measurement techniques.

The latest findings, from two sequential prospective randomized trials of intensive chemotherapy in adults aged 18-60 years with newly diagnosed AML may help clarify who will probably benefit from transplant and who won’t based on MRD status and relevant molecular features. 

The first study (AML17), conducted from 2009 to 2014, selected patients for transplant in first complete remission using a validated risk score that incorporated features including age, sex, and response after therapy. The other (AML19), conducted from 2015 to 2020, selected patients with NPM1-mutated AML for transplant only if they tested positive for MRD in peripheral blood after their second course of treatment, regardless of FLT3-ITD status or other baseline risk factors. 

Overall, the current analysis included the 737 patients with NPM1-mutated AML, 348 from AML17 and 389 from AML19, who were in complete remission after two courses of treatment and had an MRD sample at that point. 

In AML17, 27% of MRD-positive patients (16 of 60) and 18% of MRD-negative patients (52 of 288) underwent transplant in first complete remission compared with 60% (50 of 83) and 16% (49 of 306), respectively, in AML19. 

Among all 737 patients, Dr. Othman and colleagues did not observe an overall survival benefit among those who underwent transplant vs those who did not (hazard ratio [HR], 1.01) or among patients who were MRD-negative (HR, 0.82).

However, patients who were MRD-positive did have a significant survival advantage after transplant (HR, 0.39). In these patients, 3-year overall survival was 61% among those who underwent transplant vs 24% among those who did not. 

In MRD-negative patients, transplant in first complete remission did not improve overall survival despite improved relapse-free survival (HR, 0.50). This outcome, Othman explained, probably occurred because most patients who did not undergo transplant and who relapsed were salvaged, with about two thirds undergoing a transplant during their second complete response.

Results in patients with NPM1 FLT3-ITD co-mutation mirrored those in the overall population: MRD-positive patients in first complete remission who underwent transplant demonstrated improved overall survival compared with those without transplant (HR, 0.52), but the overall survival benefit did not extend to MRD-negative patients (HR, 0.80).

The findings show that molecular MRD after induction chemotherapy can identify patients with NPM1-mutated AML who are more likely to benefit from transplant in first remission, Dr. Othman concluded. However, he noted, because only 16% of patients overall were older than 60 years, the results may not be generalizable to older patients.
 

A version of this article appeared on Medscape.com.