User login
Fertility Preservation in SCD: Women Have More Complications
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
Does Acalabrutinib Fit Into Frontline MCL Therapy?
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
POLARIX: Extended Results Confirm Standard of Care for DLBCL
These findings “confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL,” said lead investigator Gilles Salles, MD, PhD, who presented the extended results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Pola-R-CHP is a modified version of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in which vincristine is replaced with polatuzumab vedotin. The modified regimen was approved by the Food and Drug Administration in April 2023 on the basis of 2-year results from the same study.
In POLARIX, researchers randomized 879 previously untreated adult patients with CD20-positive DLBCL (median age, 66 years) to six to eight 21-day cycles of treatment with either pola-R-CHP or R-CHOP. The primary endpoint was progression-free survival, and secondary endpoints included complete remission and overall survival.
The initial 2-year results — progression-free survival of 76.7% for pola-R-CHP vs 70.2% for R-CHOP — “were the first in 20 years” showing benefits for patients with DLBCL, said Salles, from Memorial Sloan Kettering Cancer Center, New York City.
In the current analysis, there were 879 patients in the global intention-to-treat population — 440 who received pola-R-CHP and 439 who received R-CHOP — and 873 in the safety analysis.
At the 5-year follow-up, Salles and colleagues observed a sustained and significant progression-free survival benefit in patients treated with pola-R-CHP, compared with those who received R-CHOP (64.9% vs 59.1%; hazard ratio [HR], 0.77).
Patients receiving the modified regimen also demonstrated significantly higher rates of complete remission at 5 years (71.8% vs 66.5%; HR, 0.75). These data tell us that for patients who reach complete remission at the end of treatment, the vast majority are still in remission at 5 years, said Salles.
For patients who did progress, those treated with pola-R-CHP had fewer subsequent therapies than those treated with R-CHOP. This included radiotherapy (9.5% vs 14.1%), systemic therapy (20.0% vs 28.2%), platinum-based therapy (9.8% vs 15.5%), stem cell transplant (5.0% vs 8.4%), chimeric antigen receptor T-cell therapy (2.3% vs 4.1%), and bispecifics (1.4% vs 2.1%).
The 5-year overall survival, a secondary endpoint, was numerically better but not significantly so among patients treated with pola-R-CHP (82.3% vs 79.5%; HR, 0.85).
In a competing risk analysis, the cumulative incidence of lymphoma-related deaths at 5 years was 9.1% with pola-R-CHP vs 12.2% with R-CHOP. The probability of non-lymphoma–related deaths, including death due to study treatment, was similar between the two groups at 5 years — 8.56% with pola-R-CHP vs 8.93% with R-CHOP.
An exploratory analysis of progression-free survival and overall survival in subgroups of the patient population, including those with high-risk disease, showed a trend in favor of pola-R-CHP in almost all cases, but Salles warned that the analysis was underpowered.
“I think that interpreting this data to decide the care of the patient should be done very cautiously,” he said.
The researchers did not observe any new safety signals, with pola-R-CHP continuing to show a favorable benefit-risk profile. Looking at adverse events of all grades, Salles noted slightly less peripheral neuropathy with pola-R-CHP (50.3% vs 52.4%), slightly more infection (47.9% vs 44.0%), as well as a favorable trend for pola-R-CHP regarding cardiac arrhythmia (3.6% vs 5.2%) and carcinogenicity (1.0% vs 2.4%), and “very slight and tiny differences” in neutropenia (48.5% vs 45.8%), anemia (33.3% vs 30.1%), and thrombocytopenia (18.0% vs 17.3%).
While the researchers concluded that the study findings confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL, Ajay Major, MD, had some reservations.
The results confirm “a small but significant benefit” in progression-free survival and no significant difference in overall survival, but there is some question as to whether pola-R-CHP is appropriate for all-comers with intermediate- or high-risk DLBCL, noted Major, a lymphoma specialist and assistant professor of medicine at the University of Colorado School of Medicine, Aurora, who was not involved in this analysis.
“The subgroup analysis in POLARIX for efficacy of pola-R-CHP based on cell of origin is not adequately powered, and further dedicated on this question studies are needed,” Major said in an interview.
One study presented at the meeting by Major’s group concluded that cell of origin is a strong predictor of the activity of pola-containing therapy in patients with relapsed/refractory large B-cell lymphoma, while another analysis of POLARIX showed progression-free survival and overall survival benefits of pola-R-CHP over R-CHOP in patients with the activated B-cell subtype of DLBCL but not those with the germinal center B-cell subtype, Major noted.
“I think many oncologists will extrapolate from these other data sources and preferentially use pola-R-CHP in patients with activated B-cell or non-germinal center DLBCL,” he predicted.
The study was funded by F. Hoffmann–La Roche/Genentech. Salles reported disclosures with the following companies: BeiGene (consultancy), AbbVie (consultancy, research funding), Genentech/Roche (consultancy, research funding), Incyte (consultancy), and BMS/Celgene (consultancy), among others. Major reported conflicts of interest with Roche/Genentech (consultancy), GSK (research funding), and Incyte (research funding).
A version of this article appeared on Medscape.com.
These findings “confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL,” said lead investigator Gilles Salles, MD, PhD, who presented the extended results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Pola-R-CHP is a modified version of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in which vincristine is replaced with polatuzumab vedotin. The modified regimen was approved by the Food and Drug Administration in April 2023 on the basis of 2-year results from the same study.
In POLARIX, researchers randomized 879 previously untreated adult patients with CD20-positive DLBCL (median age, 66 years) to six to eight 21-day cycles of treatment with either pola-R-CHP or R-CHOP. The primary endpoint was progression-free survival, and secondary endpoints included complete remission and overall survival.
The initial 2-year results — progression-free survival of 76.7% for pola-R-CHP vs 70.2% for R-CHOP — “were the first in 20 years” showing benefits for patients with DLBCL, said Salles, from Memorial Sloan Kettering Cancer Center, New York City.
In the current analysis, there were 879 patients in the global intention-to-treat population — 440 who received pola-R-CHP and 439 who received R-CHOP — and 873 in the safety analysis.
At the 5-year follow-up, Salles and colleagues observed a sustained and significant progression-free survival benefit in patients treated with pola-R-CHP, compared with those who received R-CHOP (64.9% vs 59.1%; hazard ratio [HR], 0.77).
Patients receiving the modified regimen also demonstrated significantly higher rates of complete remission at 5 years (71.8% vs 66.5%; HR, 0.75). These data tell us that for patients who reach complete remission at the end of treatment, the vast majority are still in remission at 5 years, said Salles.
For patients who did progress, those treated with pola-R-CHP had fewer subsequent therapies than those treated with R-CHOP. This included radiotherapy (9.5% vs 14.1%), systemic therapy (20.0% vs 28.2%), platinum-based therapy (9.8% vs 15.5%), stem cell transplant (5.0% vs 8.4%), chimeric antigen receptor T-cell therapy (2.3% vs 4.1%), and bispecifics (1.4% vs 2.1%).
The 5-year overall survival, a secondary endpoint, was numerically better but not significantly so among patients treated with pola-R-CHP (82.3% vs 79.5%; HR, 0.85).
In a competing risk analysis, the cumulative incidence of lymphoma-related deaths at 5 years was 9.1% with pola-R-CHP vs 12.2% with R-CHOP. The probability of non-lymphoma–related deaths, including death due to study treatment, was similar between the two groups at 5 years — 8.56% with pola-R-CHP vs 8.93% with R-CHOP.
An exploratory analysis of progression-free survival and overall survival in subgroups of the patient population, including those with high-risk disease, showed a trend in favor of pola-R-CHP in almost all cases, but Salles warned that the analysis was underpowered.
“I think that interpreting this data to decide the care of the patient should be done very cautiously,” he said.
The researchers did not observe any new safety signals, with pola-R-CHP continuing to show a favorable benefit-risk profile. Looking at adverse events of all grades, Salles noted slightly less peripheral neuropathy with pola-R-CHP (50.3% vs 52.4%), slightly more infection (47.9% vs 44.0%), as well as a favorable trend for pola-R-CHP regarding cardiac arrhythmia (3.6% vs 5.2%) and carcinogenicity (1.0% vs 2.4%), and “very slight and tiny differences” in neutropenia (48.5% vs 45.8%), anemia (33.3% vs 30.1%), and thrombocytopenia (18.0% vs 17.3%).
While the researchers concluded that the study findings confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL, Ajay Major, MD, had some reservations.
The results confirm “a small but significant benefit” in progression-free survival and no significant difference in overall survival, but there is some question as to whether pola-R-CHP is appropriate for all-comers with intermediate- or high-risk DLBCL, noted Major, a lymphoma specialist and assistant professor of medicine at the University of Colorado School of Medicine, Aurora, who was not involved in this analysis.
“The subgroup analysis in POLARIX for efficacy of pola-R-CHP based on cell of origin is not adequately powered, and further dedicated on this question studies are needed,” Major said in an interview.
One study presented at the meeting by Major’s group concluded that cell of origin is a strong predictor of the activity of pola-containing therapy in patients with relapsed/refractory large B-cell lymphoma, while another analysis of POLARIX showed progression-free survival and overall survival benefits of pola-R-CHP over R-CHOP in patients with the activated B-cell subtype of DLBCL but not those with the germinal center B-cell subtype, Major noted.
“I think many oncologists will extrapolate from these other data sources and preferentially use pola-R-CHP in patients with activated B-cell or non-germinal center DLBCL,” he predicted.
The study was funded by F. Hoffmann–La Roche/Genentech. Salles reported disclosures with the following companies: BeiGene (consultancy), AbbVie (consultancy, research funding), Genentech/Roche (consultancy, research funding), Incyte (consultancy), and BMS/Celgene (consultancy), among others. Major reported conflicts of interest with Roche/Genentech (consultancy), GSK (research funding), and Incyte (research funding).
A version of this article appeared on Medscape.com.
These findings “confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL,” said lead investigator Gilles Salles, MD, PhD, who presented the extended results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Pola-R-CHP is a modified version of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in which vincristine is replaced with polatuzumab vedotin. The modified regimen was approved by the Food and Drug Administration in April 2023 on the basis of 2-year results from the same study.
In POLARIX, researchers randomized 879 previously untreated adult patients with CD20-positive DLBCL (median age, 66 years) to six to eight 21-day cycles of treatment with either pola-R-CHP or R-CHOP. The primary endpoint was progression-free survival, and secondary endpoints included complete remission and overall survival.
The initial 2-year results — progression-free survival of 76.7% for pola-R-CHP vs 70.2% for R-CHOP — “were the first in 20 years” showing benefits for patients with DLBCL, said Salles, from Memorial Sloan Kettering Cancer Center, New York City.
In the current analysis, there were 879 patients in the global intention-to-treat population — 440 who received pola-R-CHP and 439 who received R-CHOP — and 873 in the safety analysis.
At the 5-year follow-up, Salles and colleagues observed a sustained and significant progression-free survival benefit in patients treated with pola-R-CHP, compared with those who received R-CHOP (64.9% vs 59.1%; hazard ratio [HR], 0.77).
Patients receiving the modified regimen also demonstrated significantly higher rates of complete remission at 5 years (71.8% vs 66.5%; HR, 0.75). These data tell us that for patients who reach complete remission at the end of treatment, the vast majority are still in remission at 5 years, said Salles.
For patients who did progress, those treated with pola-R-CHP had fewer subsequent therapies than those treated with R-CHOP. This included radiotherapy (9.5% vs 14.1%), systemic therapy (20.0% vs 28.2%), platinum-based therapy (9.8% vs 15.5%), stem cell transplant (5.0% vs 8.4%), chimeric antigen receptor T-cell therapy (2.3% vs 4.1%), and bispecifics (1.4% vs 2.1%).
The 5-year overall survival, a secondary endpoint, was numerically better but not significantly so among patients treated with pola-R-CHP (82.3% vs 79.5%; HR, 0.85).
In a competing risk analysis, the cumulative incidence of lymphoma-related deaths at 5 years was 9.1% with pola-R-CHP vs 12.2% with R-CHOP. The probability of non-lymphoma–related deaths, including death due to study treatment, was similar between the two groups at 5 years — 8.56% with pola-R-CHP vs 8.93% with R-CHOP.
An exploratory analysis of progression-free survival and overall survival in subgroups of the patient population, including those with high-risk disease, showed a trend in favor of pola-R-CHP in almost all cases, but Salles warned that the analysis was underpowered.
“I think that interpreting this data to decide the care of the patient should be done very cautiously,” he said.
The researchers did not observe any new safety signals, with pola-R-CHP continuing to show a favorable benefit-risk profile. Looking at adverse events of all grades, Salles noted slightly less peripheral neuropathy with pola-R-CHP (50.3% vs 52.4%), slightly more infection (47.9% vs 44.0%), as well as a favorable trend for pola-R-CHP regarding cardiac arrhythmia (3.6% vs 5.2%) and carcinogenicity (1.0% vs 2.4%), and “very slight and tiny differences” in neutropenia (48.5% vs 45.8%), anemia (33.3% vs 30.1%), and thrombocytopenia (18.0% vs 17.3%).
While the researchers concluded that the study findings confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL, Ajay Major, MD, had some reservations.
The results confirm “a small but significant benefit” in progression-free survival and no significant difference in overall survival, but there is some question as to whether pola-R-CHP is appropriate for all-comers with intermediate- or high-risk DLBCL, noted Major, a lymphoma specialist and assistant professor of medicine at the University of Colorado School of Medicine, Aurora, who was not involved in this analysis.
“The subgroup analysis in POLARIX for efficacy of pola-R-CHP based on cell of origin is not adequately powered, and further dedicated on this question studies are needed,” Major said in an interview.
One study presented at the meeting by Major’s group concluded that cell of origin is a strong predictor of the activity of pola-containing therapy in patients with relapsed/refractory large B-cell lymphoma, while another analysis of POLARIX showed progression-free survival and overall survival benefits of pola-R-CHP over R-CHOP in patients with the activated B-cell subtype of DLBCL but not those with the germinal center B-cell subtype, Major noted.
“I think many oncologists will extrapolate from these other data sources and preferentially use pola-R-CHP in patients with activated B-cell or non-germinal center DLBCL,” he predicted.
The study was funded by F. Hoffmann–La Roche/Genentech. Salles reported disclosures with the following companies: BeiGene (consultancy), AbbVie (consultancy, research funding), Genentech/Roche (consultancy, research funding), Incyte (consultancy), and BMS/Celgene (consultancy), among others. Major reported conflicts of interest with Roche/Genentech (consultancy), GSK (research funding), and Incyte (research funding).
A version of this article appeared on Medscape.com.
FROM ASH 2024
Rilzabrutinib Shines in Phase 3 Trial of Tough-to-Treat Immune Thrombocytopenia
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
Epcore NHL-1 Update: Treatment Effective Before CAR T
These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.
This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference.
With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.
In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.
Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.
In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.
Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.
At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.
The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%.
Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.
“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.
Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.
This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference.
With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.
In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.
Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.
In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.
Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.
At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.
The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%.
Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.
“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.
Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.
This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference.
With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.
In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.
Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.
In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.
Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.
At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.
The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%.
Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.
“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.
Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
With Chemo, Blinatumomab Boosts DFS in Pediatric B-ALL
Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.
As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”
The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average.
The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug.
Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black.
The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001).
In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively.
Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.
“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said.
“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”
Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said.
“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy.
“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said.
As for method of delivery, Rau said easier-to-deliver formulations are in development.
Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.
As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”
The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average.
The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug.
Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black.
The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001).
In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively.
Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.
“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said.
“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”
Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said.
“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy.
“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said.
As for method of delivery, Rau said easier-to-deliver formulations are in development.
Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.
As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”
The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average.
The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug.
Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black.
The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001).
In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively.
Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.
“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said.
“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”
Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said.
“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy.
“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said.
As for method of delivery, Rau said easier-to-deliver formulations are in development.
Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
High-Fiber Diet Linked to Improved Stem Cell Transplant, GvHD Outcomes
Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits.
“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.
Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.
Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.
However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.
For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.
Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration.
Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).
After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health.
Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).
Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD.
Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).
However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).
A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.
The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.
“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview.
“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.
“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”
Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.
The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.
“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.
“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.
Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned.
“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said.
High-Fiber Diet Slows MM Disease Progression?
The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).
NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.
Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m2 or higher.
The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI.
Notably, two patients in the study had stabilization of disease progression.
“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement.
“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.
The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.
Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not.
“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.
The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.
A version of this article first appeared on Medscape.com.
Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits.
“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.
Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.
Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.
However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.
For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.
Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration.
Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).
After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health.
Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).
Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD.
Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).
However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).
A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.
The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.
“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview.
“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.
“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”
Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.
The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.
“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.
“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.
Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned.
“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said.
High-Fiber Diet Slows MM Disease Progression?
The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).
NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.
Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m2 or higher.
The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI.
Notably, two patients in the study had stabilization of disease progression.
“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement.
“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.
The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.
Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not.
“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.
The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.
A version of this article first appeared on Medscape.com.
Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits.
“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.
Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.
Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.
However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.
For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.
Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration.
Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).
After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health.
Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).
Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD.
Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).
However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).
A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.
The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.
“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview.
“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.
“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”
Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.
The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.
“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.
“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.
Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned.
“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said.
High-Fiber Diet Slows MM Disease Progression?
The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).
NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.
Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m2 or higher.
The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI.
Notably, two patients in the study had stabilization of disease progression.
“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement.
“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.
The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.
Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not.
“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.
The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
24-Hour Urine Testing in Multiple Myeloma: Time to Stop?
Overall, evaluating patients’ responses using urine-free and traditional criteria led to nearly identical assessments. When comparing the two criteria, only 7 of 645 patients evaluated had discordant results.
The findings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting, add weight to the push to drop the requirement to perform routine urine tests from International Myeloma Working Group (IMWG) response criteria for multiple myeloma, said the study’s lead author, Rahul Banerjee, MD, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle.
“International guidelines for multiple myeloma, which haven’t been updated in almost a decade, currently recommend these refrigerated 24-hour urine assessments, which are cumbersome for patients and can create substantial disparities,” Banerjee said in an interview.
“The international community is actually in the midst of updating its guidelines (I am part of this effort), and our work will hopefully help lead the way for future guidelines that de-emphasize the need for 24-hour urine testing to only a few rare scenarios, such as AL amyloidosis,” Banerjee added.
Urine tests can help detect the presence of abnormal proteins, which can indicate the level of myeloma tumor burden. Performing these tests routinely can help physicians monitor the effectiveness of patients’ treatment in practice and clinical trials.
Some recent data, however, suggest that dropping urine testing from the response criteria would change the response assessment in fewer than 5% of patients. Still, it’s not clear how urine-free criteria would impact assessments of progression free survival.
In the current study, Banerjee and colleagues performed a secondary analysis of the STaMINA trial. In the original trial, patients were randomized to lenalidomide maintenance, tandem autologous hematopoietic cell transplantation followed by lenalidomide maintenance, or consolidation therapy (lenalidomide, bortezomib, and dexamethasone) followed by lenalidomide maintenance until disease progression.
The secondary analysis included 645 patients from the original trial who were evaluable 56 days following autologous hematopoietic cell transplantation. The analysis looked at patients across all groups, but excluded those with progressive disease, and compared patients’ responses using traditional IMWG criteria, which includes 24-hour urine assessments, and urine-free criteria. Response measurements included complete response, very good partial response, partial response, and stable disease.
Patients were a median age of 56 years, 41% were female, 17% were Black, and 7% were Hispanic; 26% had light-chain only disease. About half (49%) had received lenalidomide alone, 28% had received post-autologous stem cell transplantation consolidation followed by lenalidomide, and 24% had received tandem transplantation followed by lenalidomide.
The analysis showed that “urine-free response criteria worked just fine in terms of their prognostic value,” Banerjee said while presenting the findings.
Specifically, the complete response rate was 29.4% using the traditional criteria vs 29.7% using the urine-free criteria. The very good partial response rate was 37.0% with the traditional approach vs 36.6% with the urine-free approach. The partial response rate was 30.7% for both and the stable disease rate was 3.0% for both.
Achieving a complete response based on the urine-free criteria was highly prognostic for progression-free survival (P = .005) while achieving a very good partial response by either criterion was borderline prognostic for progression-free survival (P = .102).
Only 1.1% of patients — seven patients altogether — had discordant responses between traditional and urine-free response criteria, Banerjee noted. One patient, for instance, was downgraded from a very good partial response with traditional criteria to a partial response with urine-free criteria “because current response criteria rate urine [as] more important than serum-free light chains,” Banerjee explained. Two other patients who met all other stringent criteria for a complete response but still had urine paraprotein at Day 56 were classified as having a very good partial response using traditional criteria but as a complete response with the urine-free criteria.
The other four patients with discordant results were the most important, Banerjee said. These patients were missing urine protein electrophoresis values, which made them non-evaluable using traditional criteria, but became evaluable when using urine-free criteria. “This is, I think, the bane of our existence, right? We ask our patients to put their blood, soul, sweat, and tears into being in a clinical trial, and then they’re not evaluable,” he said.
Overall, these results strongly support the de-emphasis of 24-hour urine requirements in updated IMWG response criteria, said Banerjee. However, he noted, 24-hour urine testing still has a very important place in the screening process and in patients with monoclonal gammopathy of renal significance or AL amyloidosis.
“This study provides reassurance to those of us already not repeating urine tests that urine testing is unnecessary for tracking responses,” said Manni Mohyuddin, MD, from the Multiple Myeloma Program at Huntsman Cancer Institute and assistant professor at the University of Utah, Salt Lake City. “These assessments aren’t done consistently in practice outside of trials anyway, and I hope that this study will lead to a formal change in criteria and the omission of urine assessments in clinical trials.”
Funding for the study was provided by the National Heart, Lung, and Blood Institute; National Cancer Institute; Alliance for Clinical Trials in Oncology; ECOG-ACRIN Cancer Research Group; and SWOG; and contributions were provided by Celgene and Millennium Pharmaceuticals. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol-Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures, and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi. Mohyuddin has disclosed no personal payments and no consultation for industry. His institution has received research funding from Janssen for his role as a principal investigator on a trial.
A version of this article first appeared on Medscape.com.
Overall, evaluating patients’ responses using urine-free and traditional criteria led to nearly identical assessments. When comparing the two criteria, only 7 of 645 patients evaluated had discordant results.
The findings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting, add weight to the push to drop the requirement to perform routine urine tests from International Myeloma Working Group (IMWG) response criteria for multiple myeloma, said the study’s lead author, Rahul Banerjee, MD, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle.
“International guidelines for multiple myeloma, which haven’t been updated in almost a decade, currently recommend these refrigerated 24-hour urine assessments, which are cumbersome for patients and can create substantial disparities,” Banerjee said in an interview.
“The international community is actually in the midst of updating its guidelines (I am part of this effort), and our work will hopefully help lead the way for future guidelines that de-emphasize the need for 24-hour urine testing to only a few rare scenarios, such as AL amyloidosis,” Banerjee added.
Urine tests can help detect the presence of abnormal proteins, which can indicate the level of myeloma tumor burden. Performing these tests routinely can help physicians monitor the effectiveness of patients’ treatment in practice and clinical trials.
Some recent data, however, suggest that dropping urine testing from the response criteria would change the response assessment in fewer than 5% of patients. Still, it’s not clear how urine-free criteria would impact assessments of progression free survival.
In the current study, Banerjee and colleagues performed a secondary analysis of the STaMINA trial. In the original trial, patients were randomized to lenalidomide maintenance, tandem autologous hematopoietic cell transplantation followed by lenalidomide maintenance, or consolidation therapy (lenalidomide, bortezomib, and dexamethasone) followed by lenalidomide maintenance until disease progression.
The secondary analysis included 645 patients from the original trial who were evaluable 56 days following autologous hematopoietic cell transplantation. The analysis looked at patients across all groups, but excluded those with progressive disease, and compared patients’ responses using traditional IMWG criteria, which includes 24-hour urine assessments, and urine-free criteria. Response measurements included complete response, very good partial response, partial response, and stable disease.
Patients were a median age of 56 years, 41% were female, 17% were Black, and 7% were Hispanic; 26% had light-chain only disease. About half (49%) had received lenalidomide alone, 28% had received post-autologous stem cell transplantation consolidation followed by lenalidomide, and 24% had received tandem transplantation followed by lenalidomide.
The analysis showed that “urine-free response criteria worked just fine in terms of their prognostic value,” Banerjee said while presenting the findings.
Specifically, the complete response rate was 29.4% using the traditional criteria vs 29.7% using the urine-free criteria. The very good partial response rate was 37.0% with the traditional approach vs 36.6% with the urine-free approach. The partial response rate was 30.7% for both and the stable disease rate was 3.0% for both.
Achieving a complete response based on the urine-free criteria was highly prognostic for progression-free survival (P = .005) while achieving a very good partial response by either criterion was borderline prognostic for progression-free survival (P = .102).
Only 1.1% of patients — seven patients altogether — had discordant responses between traditional and urine-free response criteria, Banerjee noted. One patient, for instance, was downgraded from a very good partial response with traditional criteria to a partial response with urine-free criteria “because current response criteria rate urine [as] more important than serum-free light chains,” Banerjee explained. Two other patients who met all other stringent criteria for a complete response but still had urine paraprotein at Day 56 were classified as having a very good partial response using traditional criteria but as a complete response with the urine-free criteria.
The other four patients with discordant results were the most important, Banerjee said. These patients were missing urine protein electrophoresis values, which made them non-evaluable using traditional criteria, but became evaluable when using urine-free criteria. “This is, I think, the bane of our existence, right? We ask our patients to put their blood, soul, sweat, and tears into being in a clinical trial, and then they’re not evaluable,” he said.
Overall, these results strongly support the de-emphasis of 24-hour urine requirements in updated IMWG response criteria, said Banerjee. However, he noted, 24-hour urine testing still has a very important place in the screening process and in patients with monoclonal gammopathy of renal significance or AL amyloidosis.
“This study provides reassurance to those of us already not repeating urine tests that urine testing is unnecessary for tracking responses,” said Manni Mohyuddin, MD, from the Multiple Myeloma Program at Huntsman Cancer Institute and assistant professor at the University of Utah, Salt Lake City. “These assessments aren’t done consistently in practice outside of trials anyway, and I hope that this study will lead to a formal change in criteria and the omission of urine assessments in clinical trials.”
Funding for the study was provided by the National Heart, Lung, and Blood Institute; National Cancer Institute; Alliance for Clinical Trials in Oncology; ECOG-ACRIN Cancer Research Group; and SWOG; and contributions were provided by Celgene and Millennium Pharmaceuticals. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol-Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures, and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi. Mohyuddin has disclosed no personal payments and no consultation for industry. His institution has received research funding from Janssen for his role as a principal investigator on a trial.
A version of this article first appeared on Medscape.com.
Overall, evaluating patients’ responses using urine-free and traditional criteria led to nearly identical assessments. When comparing the two criteria, only 7 of 645 patients evaluated had discordant results.
The findings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting, add weight to the push to drop the requirement to perform routine urine tests from International Myeloma Working Group (IMWG) response criteria for multiple myeloma, said the study’s lead author, Rahul Banerjee, MD, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle.
“International guidelines for multiple myeloma, which haven’t been updated in almost a decade, currently recommend these refrigerated 24-hour urine assessments, which are cumbersome for patients and can create substantial disparities,” Banerjee said in an interview.
“The international community is actually in the midst of updating its guidelines (I am part of this effort), and our work will hopefully help lead the way for future guidelines that de-emphasize the need for 24-hour urine testing to only a few rare scenarios, such as AL amyloidosis,” Banerjee added.
Urine tests can help detect the presence of abnormal proteins, which can indicate the level of myeloma tumor burden. Performing these tests routinely can help physicians monitor the effectiveness of patients’ treatment in practice and clinical trials.
Some recent data, however, suggest that dropping urine testing from the response criteria would change the response assessment in fewer than 5% of patients. Still, it’s not clear how urine-free criteria would impact assessments of progression free survival.
In the current study, Banerjee and colleagues performed a secondary analysis of the STaMINA trial. In the original trial, patients were randomized to lenalidomide maintenance, tandem autologous hematopoietic cell transplantation followed by lenalidomide maintenance, or consolidation therapy (lenalidomide, bortezomib, and dexamethasone) followed by lenalidomide maintenance until disease progression.
The secondary analysis included 645 patients from the original trial who were evaluable 56 days following autologous hematopoietic cell transplantation. The analysis looked at patients across all groups, but excluded those with progressive disease, and compared patients’ responses using traditional IMWG criteria, which includes 24-hour urine assessments, and urine-free criteria. Response measurements included complete response, very good partial response, partial response, and stable disease.
Patients were a median age of 56 years, 41% were female, 17% were Black, and 7% were Hispanic; 26% had light-chain only disease. About half (49%) had received lenalidomide alone, 28% had received post-autologous stem cell transplantation consolidation followed by lenalidomide, and 24% had received tandem transplantation followed by lenalidomide.
The analysis showed that “urine-free response criteria worked just fine in terms of their prognostic value,” Banerjee said while presenting the findings.
Specifically, the complete response rate was 29.4% using the traditional criteria vs 29.7% using the urine-free criteria. The very good partial response rate was 37.0% with the traditional approach vs 36.6% with the urine-free approach. The partial response rate was 30.7% for both and the stable disease rate was 3.0% for both.
Achieving a complete response based on the urine-free criteria was highly prognostic for progression-free survival (P = .005) while achieving a very good partial response by either criterion was borderline prognostic for progression-free survival (P = .102).
Only 1.1% of patients — seven patients altogether — had discordant responses between traditional and urine-free response criteria, Banerjee noted. One patient, for instance, was downgraded from a very good partial response with traditional criteria to a partial response with urine-free criteria “because current response criteria rate urine [as] more important than serum-free light chains,” Banerjee explained. Two other patients who met all other stringent criteria for a complete response but still had urine paraprotein at Day 56 were classified as having a very good partial response using traditional criteria but as a complete response with the urine-free criteria.
The other four patients with discordant results were the most important, Banerjee said. These patients were missing urine protein electrophoresis values, which made them non-evaluable using traditional criteria, but became evaluable when using urine-free criteria. “This is, I think, the bane of our existence, right? We ask our patients to put their blood, soul, sweat, and tears into being in a clinical trial, and then they’re not evaluable,” he said.
Overall, these results strongly support the de-emphasis of 24-hour urine requirements in updated IMWG response criteria, said Banerjee. However, he noted, 24-hour urine testing still has a very important place in the screening process and in patients with monoclonal gammopathy of renal significance or AL amyloidosis.
“This study provides reassurance to those of us already not repeating urine tests that urine testing is unnecessary for tracking responses,” said Manni Mohyuddin, MD, from the Multiple Myeloma Program at Huntsman Cancer Institute and assistant professor at the University of Utah, Salt Lake City. “These assessments aren’t done consistently in practice outside of trials anyway, and I hope that this study will lead to a formal change in criteria and the omission of urine assessments in clinical trials.”
Funding for the study was provided by the National Heart, Lung, and Blood Institute; National Cancer Institute; Alliance for Clinical Trials in Oncology; ECOG-ACRIN Cancer Research Group; and SWOG; and contributions were provided by Celgene and Millennium Pharmaceuticals. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol-Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures, and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi. Mohyuddin has disclosed no personal payments and no consultation for industry. His institution has received research funding from Janssen for his role as a principal investigator on a trial.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
IVIG Prophylaxis in Multiple Myeloma Cuts Infections, Boosts Survival
Among 225 consecutive patients who received at least one treatment for relapsed and/or refractory multiple myeloma, those who received IVIG prophylaxis experienced a significantly longer duration of infection-free survival and an almost threefold longer median overall survival, compared with patients who did not receive IVIG prophylaxis.
IVIG supplementation has been shown to prevent severe infections in patients with multiple myeloma, but evidence on the best time to initiate IVIG prophylaxis among those receiving teclistamab remains less clear.
“Our institutional practice is to start IVIG about cycle 2 of therapy, which ended up being around 39 days,” but a key takeaway from the current findings is to “start IVIG within 30 days,” said lead investigator Heloise Cheruvalath, BA, a medical student at Medical College of Wisconsin, Milwaukee, who presented the findings.
The 225 patients included in the study had received at least one dose of standard-of-care teclistamab or an investigational B-cell maturation antigen (BCMA)–directed bispecific antibody (bsAb). IVIG was given as prophylaxis to 92 patients (41%) in the primary arm. The remaining 133 patients (59%) did not receive IVIG prophylaxis, but 29% received IVIG after a documented infection.
In total, there were 288 infections in 136 patients, and about 61% of infections required hospitalization. Median time to infection was 97 days, with the 12-month cumulative incidence of all-grade infections reaching 73% and the incidence of grade 3 or higher infections totaling 53%. Respiratory tract infections were the most common infection type, with COVID-19 accounting for 11% of cases, Cheruvalath noted.
Comparing patients who did and did not receive IVIG prophylaxis, median infection-free survival was significantly longer in the prophylaxis group — a median of 7.7 months vs 3 months — as was grade 3 or higher infection-free survival — a median of 14 months vs 7.5 months.
IVIG prophylaxis also led to a higher rate of 2-year progression free survival in the prophylaxis vs nonprophylaxis group — at 38% vs 32% — as well as longer median progression-free survival — at 15 months vs 8 months.
After multivariate analysis, IVIG prophylaxis was no longer significantly associated with improved progression-free survival.
However, median overall survival did remain significantly better in the IVIG prophylaxis than the nonprophylaxis group after multivariate analysis — 44 months vs 16 months. The presence of high-risk and extramedullary disease was independently associated with worse overall survival.
The effects of IVIG prophylaxis were stronger for bacterial infections at earlier (30 days or sooner) vs later (31 days or later) time points, but timing of IVIG therapy did not appear to affect the incidence of viral infections.
A study limitation was lack of randomization; IVIG prophylaxis was given at the physician’s discretion. In addition, multiple myeloma treatment was not standardized, with 15% of IVIG patients and 38% of non-IVIG patients receiving investigational BCMA bsAB.
“However, the majority of those who received primary IVIG prophylaxis were treated with standard-of-care teclistamab, making our results generalizable to current clinical practice,” Cheruvalath said.
Rahul Banerjee, MD, who was not involved with the research, noted he has already started providing routine IVIG prophylaxis based on earlier research from this group. “Before I did, my patients would often get very rare infections requiring protracted courses of antibiotics,” Banerjee, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle, said in an interview. “Moving to IVIG before the infections start makes much more sense.”
Banerjee also commented that, in general, “the myeloma field has been moving from IV treatments to subcutaneous treatments to lower ‘time toxicity’ and IVIG is a notable exception to that trend, but perhaps it won’t be this way forever.”
Many patients with rheumatologic conditions receive subcutaneous immunoglobulin, in some cases, with kits they can self-administer at home, Banerjee said, and “I know some groups are starting to work on moving subcutaneous immunoglobulin to the oncologic setting.”
Funding was provided by the Advancing Healthier Wisconsin Endowment. Cheruvalath has reported no relevant disclosures. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures; and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi.
A version of this article first appeared on Medscape.com.
Among 225 consecutive patients who received at least one treatment for relapsed and/or refractory multiple myeloma, those who received IVIG prophylaxis experienced a significantly longer duration of infection-free survival and an almost threefold longer median overall survival, compared with patients who did not receive IVIG prophylaxis.
IVIG supplementation has been shown to prevent severe infections in patients with multiple myeloma, but evidence on the best time to initiate IVIG prophylaxis among those receiving teclistamab remains less clear.
“Our institutional practice is to start IVIG about cycle 2 of therapy, which ended up being around 39 days,” but a key takeaway from the current findings is to “start IVIG within 30 days,” said lead investigator Heloise Cheruvalath, BA, a medical student at Medical College of Wisconsin, Milwaukee, who presented the findings.
The 225 patients included in the study had received at least one dose of standard-of-care teclistamab or an investigational B-cell maturation antigen (BCMA)–directed bispecific antibody (bsAb). IVIG was given as prophylaxis to 92 patients (41%) in the primary arm. The remaining 133 patients (59%) did not receive IVIG prophylaxis, but 29% received IVIG after a documented infection.
In total, there were 288 infections in 136 patients, and about 61% of infections required hospitalization. Median time to infection was 97 days, with the 12-month cumulative incidence of all-grade infections reaching 73% and the incidence of grade 3 or higher infections totaling 53%. Respiratory tract infections were the most common infection type, with COVID-19 accounting for 11% of cases, Cheruvalath noted.
Comparing patients who did and did not receive IVIG prophylaxis, median infection-free survival was significantly longer in the prophylaxis group — a median of 7.7 months vs 3 months — as was grade 3 or higher infection-free survival — a median of 14 months vs 7.5 months.
IVIG prophylaxis also led to a higher rate of 2-year progression free survival in the prophylaxis vs nonprophylaxis group — at 38% vs 32% — as well as longer median progression-free survival — at 15 months vs 8 months.
After multivariate analysis, IVIG prophylaxis was no longer significantly associated with improved progression-free survival.
However, median overall survival did remain significantly better in the IVIG prophylaxis than the nonprophylaxis group after multivariate analysis — 44 months vs 16 months. The presence of high-risk and extramedullary disease was independently associated with worse overall survival.
The effects of IVIG prophylaxis were stronger for bacterial infections at earlier (30 days or sooner) vs later (31 days or later) time points, but timing of IVIG therapy did not appear to affect the incidence of viral infections.
A study limitation was lack of randomization; IVIG prophylaxis was given at the physician’s discretion. In addition, multiple myeloma treatment was not standardized, with 15% of IVIG patients and 38% of non-IVIG patients receiving investigational BCMA bsAB.
“However, the majority of those who received primary IVIG prophylaxis were treated with standard-of-care teclistamab, making our results generalizable to current clinical practice,” Cheruvalath said.
Rahul Banerjee, MD, who was not involved with the research, noted he has already started providing routine IVIG prophylaxis based on earlier research from this group. “Before I did, my patients would often get very rare infections requiring protracted courses of antibiotics,” Banerjee, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle, said in an interview. “Moving to IVIG before the infections start makes much more sense.”
Banerjee also commented that, in general, “the myeloma field has been moving from IV treatments to subcutaneous treatments to lower ‘time toxicity’ and IVIG is a notable exception to that trend, but perhaps it won’t be this way forever.”
Many patients with rheumatologic conditions receive subcutaneous immunoglobulin, in some cases, with kits they can self-administer at home, Banerjee said, and “I know some groups are starting to work on moving subcutaneous immunoglobulin to the oncologic setting.”
Funding was provided by the Advancing Healthier Wisconsin Endowment. Cheruvalath has reported no relevant disclosures. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures; and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi.
A version of this article first appeared on Medscape.com.
Among 225 consecutive patients who received at least one treatment for relapsed and/or refractory multiple myeloma, those who received IVIG prophylaxis experienced a significantly longer duration of infection-free survival and an almost threefold longer median overall survival, compared with patients who did not receive IVIG prophylaxis.
IVIG supplementation has been shown to prevent severe infections in patients with multiple myeloma, but evidence on the best time to initiate IVIG prophylaxis among those receiving teclistamab remains less clear.
“Our institutional practice is to start IVIG about cycle 2 of therapy, which ended up being around 39 days,” but a key takeaway from the current findings is to “start IVIG within 30 days,” said lead investigator Heloise Cheruvalath, BA, a medical student at Medical College of Wisconsin, Milwaukee, who presented the findings.
The 225 patients included in the study had received at least one dose of standard-of-care teclistamab or an investigational B-cell maturation antigen (BCMA)–directed bispecific antibody (bsAb). IVIG was given as prophylaxis to 92 patients (41%) in the primary arm. The remaining 133 patients (59%) did not receive IVIG prophylaxis, but 29% received IVIG after a documented infection.
In total, there were 288 infections in 136 patients, and about 61% of infections required hospitalization. Median time to infection was 97 days, with the 12-month cumulative incidence of all-grade infections reaching 73% and the incidence of grade 3 or higher infections totaling 53%. Respiratory tract infections were the most common infection type, with COVID-19 accounting for 11% of cases, Cheruvalath noted.
Comparing patients who did and did not receive IVIG prophylaxis, median infection-free survival was significantly longer in the prophylaxis group — a median of 7.7 months vs 3 months — as was grade 3 or higher infection-free survival — a median of 14 months vs 7.5 months.
IVIG prophylaxis also led to a higher rate of 2-year progression free survival in the prophylaxis vs nonprophylaxis group — at 38% vs 32% — as well as longer median progression-free survival — at 15 months vs 8 months.
After multivariate analysis, IVIG prophylaxis was no longer significantly associated with improved progression-free survival.
However, median overall survival did remain significantly better in the IVIG prophylaxis than the nonprophylaxis group after multivariate analysis — 44 months vs 16 months. The presence of high-risk and extramedullary disease was independently associated with worse overall survival.
The effects of IVIG prophylaxis were stronger for bacterial infections at earlier (30 days or sooner) vs later (31 days or later) time points, but timing of IVIG therapy did not appear to affect the incidence of viral infections.
A study limitation was lack of randomization; IVIG prophylaxis was given at the physician’s discretion. In addition, multiple myeloma treatment was not standardized, with 15% of IVIG patients and 38% of non-IVIG patients receiving investigational BCMA bsAB.
“However, the majority of those who received primary IVIG prophylaxis were treated with standard-of-care teclistamab, making our results generalizable to current clinical practice,” Cheruvalath said.
Rahul Banerjee, MD, who was not involved with the research, noted he has already started providing routine IVIG prophylaxis based on earlier research from this group. “Before I did, my patients would often get very rare infections requiring protracted courses of antibiotics,” Banerjee, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle, said in an interview. “Moving to IVIG before the infections start makes much more sense.”
Banerjee also commented that, in general, “the myeloma field has been moving from IV treatments to subcutaneous treatments to lower ‘time toxicity’ and IVIG is a notable exception to that trend, but perhaps it won’t be this way forever.”
Many patients with rheumatologic conditions receive subcutaneous immunoglobulin, in some cases, with kits they can self-administer at home, Banerjee said, and “I know some groups are starting to work on moving subcutaneous immunoglobulin to the oncologic setting.”
Funding was provided by the Advancing Healthier Wisconsin Endowment. Cheruvalath has reported no relevant disclosures. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures; and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
LBCL: Bispecific Antibodies Fare Less Well in Real-World Analysis
In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached).
It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”
He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”
According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”
The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023.
“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”
The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).
“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.
In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%).
The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.”
Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.
“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”
In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”
Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”
In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work.
“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.”
He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”
Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.”
Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”
There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.
A version of this article first appeared on Medscape.com.
In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached).
It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”
He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”
According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”
The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023.
“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”
The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).
“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.
In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%).
The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.”
Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.
“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”
In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”
Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”
In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work.
“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.”
He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”
Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.”
Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”
There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.
A version of this article first appeared on Medscape.com.
In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached).
It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”
He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”
According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”
The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023.
“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”
The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).
“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.
In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%).
The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.”
Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.
“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”
In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”
Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”
In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work.
“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.”
He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”
Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.”
Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”
There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.
A version of this article first appeared on Medscape.com.
FROM ASH 2024