Sharon Worcester, MA

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

Jeffrey S. Weber, MD, PhD, the 2016 winner of the Giants of Cancer Care award in melanoma and a valued contributor to Medscape Oncology, has died.

Dr. Weber, a melanoma and cancer immunotherapy specialist, served as deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University (NYU) Langone Medical Center in New York City. He also held positions as the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at the NYU Grossman School of Medicine, director of the Experimental Therapeutics Program, and co-leader of the Clinical Melanoma Program Board at NYU Langone Health.

Dr. Weber was a principal investigator on many studies, including pivotal clinical drug trials in melanoma and trials focused on managing autoimmune side effects from immunotherapy. He published more than 150 articles in top peer-reviewed journals.

For many years, Dr. Weber hosted the popular “Weber on Oncology” series of video contributions for Medscape Oncology, sharing updates and insights on noteworthy research and breakthroughs in melanoma.

“The Melanoma Research Alliance mourns the passing of Dr. Jeffrey S. Weber, a true pioneer in the field of cancer immunotherapy and an extraordinary leader in melanoma research. His contributions have forever changed the landscape of melanoma treatment, bringing groundbreaking advances from the lab into clinical practice and offering hope to countless patients,” the Melanoma Research Alliance posted on LinkedIn. 

Many X users also shared condolences and memories of Dr. Weber, praising his numerous contributions and accomplishments. 

“[Cancer Research Institute] mourns the loss of Dr. Jeffrey S. Weber ... [a]s an accomplished physician scientist, Dr. Weber drove advances in melanoma research, and played an active role in educating patients about the lifesaving power of immunotherapy,” the Cancer Research Institute posted.

A colleague noted that “[h]e was involved in the early days of cytokine and cell therapy and most recently led studies of personalized vaccines for melanoma patients. ... He was a great friend and colleague to many of us in the melanoma and immunotherapy field and we will remember him as a pioneer, thought leader and compassionate physician.”

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

Jeffrey S. Weber, MD, PhD, the 2016 winner of the Giants of Cancer Care award in melanoma and a valued contributor to Medscape Oncology, has died.

Dr. Weber, a melanoma and cancer immunotherapy specialist, served as deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University (NYU) Langone Medical Center in New York City. He also held positions as the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at the NYU Grossman School of Medicine, director of the Experimental Therapeutics Program, and co-leader of the Clinical Melanoma Program Board at NYU Langone Health.

Dr. Weber was a principal investigator on many studies, including pivotal clinical drug trials in melanoma and trials focused on managing autoimmune side effects from immunotherapy. He published more than 150 articles in top peer-reviewed journals.

For many years, Dr. Weber hosted the popular “Weber on Oncology” series of video contributions for Medscape Oncology, sharing updates and insights on noteworthy research and breakthroughs in melanoma.

“The Melanoma Research Alliance mourns the passing of Dr. Jeffrey S. Weber, a true pioneer in the field of cancer immunotherapy and an extraordinary leader in melanoma research. His contributions have forever changed the landscape of melanoma treatment, bringing groundbreaking advances from the lab into clinical practice and offering hope to countless patients,” the Melanoma Research Alliance posted on LinkedIn. 

Many X users also shared condolences and memories of Dr. Weber, praising his numerous contributions and accomplishments. 

“[Cancer Research Institute] mourns the loss of Dr. Jeffrey S. Weber ... [a]s an accomplished physician scientist, Dr. Weber drove advances in melanoma research, and played an active role in educating patients about the lifesaving power of immunotherapy,” the Cancer Research Institute posted.

A colleague noted that “[h]e was involved in the early days of cytokine and cell therapy and most recently led studies of personalized vaccines for melanoma patients. ... He was a great friend and colleague to many of us in the melanoma and immunotherapy field and we will remember him as a pioneer, thought leader and compassionate physician.”

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

Jeffrey S. Weber, MD, PhD, the 2016 winner of the Giants of Cancer Care award in melanoma and a valued contributor to Medscape Oncology, has died.

Dr. Weber, a melanoma and cancer immunotherapy specialist, served as deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University (NYU) Langone Medical Center in New York City. He also held positions as the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at the NYU Grossman School of Medicine, director of the Experimental Therapeutics Program, and co-leader of the Clinical Melanoma Program Board at NYU Langone Health.

Dr. Weber was a principal investigator on many studies, including pivotal clinical drug trials in melanoma and trials focused on managing autoimmune side effects from immunotherapy. He published more than 150 articles in top peer-reviewed journals.

For many years, Dr. Weber hosted the popular “Weber on Oncology” series of video contributions for Medscape Oncology, sharing updates and insights on noteworthy research and breakthroughs in melanoma.

“The Melanoma Research Alliance mourns the passing of Dr. Jeffrey S. Weber, a true pioneer in the field of cancer immunotherapy and an extraordinary leader in melanoma research. His contributions have forever changed the landscape of melanoma treatment, bringing groundbreaking advances from the lab into clinical practice and offering hope to countless patients,” the Melanoma Research Alliance posted on LinkedIn. 

Many X users also shared condolences and memories of Dr. Weber, praising his numerous contributions and accomplishments. 

“[Cancer Research Institute] mourns the loss of Dr. Jeffrey S. Weber ... [a]s an accomplished physician scientist, Dr. Weber drove advances in melanoma research, and played an active role in educating patients about the lifesaving power of immunotherapy,” the Cancer Research Institute posted.

A colleague noted that “[h]e was involved in the early days of cytokine and cell therapy and most recently led studies of personalized vaccines for melanoma patients. ... He was a great friend and colleague to many of us in the melanoma and immunotherapy field and we will remember him as a pioneer, thought leader and compassionate physician.”

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

The US Food and Drug Administration (FDA) has approved axatilimab (Niktimvo, Incyte Corporation and Syndax) for the treatment of adult and pediatric patients with chronic graft versus host disease (GVHD) who have not responded to at least two prior lines of systemic therapy and who weigh ≥ 40 kg.

Chronic GVHD is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation that develops in about 50% of transplant recipients.

The first-in-class treatment for chronic GVHD is a monoclonal antibody that targets the colony-stimulating factor 1 (CSF-1) receptor. Approval for axatilimab followed priority review of Incyte’s Biologic License Application and was based on findings from the open-label phase 2 AGAVE-201 trial. 

Study participants had chronic GVHD after allogeneic hematopoietic stem cell transplantation and had failed to respond to at least two prior lines of systemic therapy (median, four lines of therapy). Prior therapies included ruxolitinib, belumosudil, and ibrutinib in 74%, 23%, and 31% of patients, respectively. Overall, 239 patients were enrolled at 121 study sites and were randomly assigned 1:1:1 to three doses.

The FDA recommended dose of axatilimab is 0.3 mg/kg (to a maximum of 35 mg) as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. Other doses tested in the AGAVE-201 trial were 1 mg/kg every 2 weeks and 3 mg/kg every 4 weeks. 

The trial measured overall response rate over the first six cycles (24 weeks). In the 79 patients who received the recommended 0.3-mg/kg dose, the overall response rate was 75%, and the median time to first response was 1.5 months (range, 0.9-5.1). The median duration of response — measured from first response to progression, death, or switch to a new systemic therapy for chronic GVHD — was 1.9 months. 

In those who responded to the therapy, there were no deaths or new therapies required in 60% of patients.

The most common adverse reactions, occurring in 15% or more patients, included increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, nausea, headache, diarrhea, cough, pyrexia, and dyspnea. 

In the AGAVE-201 trial results, researchers noted that drug discontinuation from treatment-emergent adverse events occurred in 6% of patients in the 0.3-mg/kg cohort, in 22% in the 1-mg/kg cohort, and in 18% in the 3-mg/kg cohort. Fatal treatment-emergent adverse events occurred in 1.3% of patients in the 0.3-mg/kg cohort. 

“Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” lead study author Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg, Germany, said in a company press release. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pretreated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

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

The US Food and Drug Administration (FDA) has approved axatilimab (Niktimvo, Incyte Corporation and Syndax) for the treatment of adult and pediatric patients with chronic graft versus host disease (GVHD) who have not responded to at least two prior lines of systemic therapy and who weigh ≥ 40 kg.

Chronic GVHD is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation that develops in about 50% of transplant recipients.

The first-in-class treatment for chronic GVHD is a monoclonal antibody that targets the colony-stimulating factor 1 (CSF-1) receptor. Approval for axatilimab followed priority review of Incyte’s Biologic License Application and was based on findings from the open-label phase 2 AGAVE-201 trial. 

Study participants had chronic GVHD after allogeneic hematopoietic stem cell transplantation and had failed to respond to at least two prior lines of systemic therapy (median, four lines of therapy). Prior therapies included ruxolitinib, belumosudil, and ibrutinib in 74%, 23%, and 31% of patients, respectively. Overall, 239 patients were enrolled at 121 study sites and were randomly assigned 1:1:1 to three doses.

The FDA recommended dose of axatilimab is 0.3 mg/kg (to a maximum of 35 mg) as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. Other doses tested in the AGAVE-201 trial were 1 mg/kg every 2 weeks and 3 mg/kg every 4 weeks. 

The trial measured overall response rate over the first six cycles (24 weeks). In the 79 patients who received the recommended 0.3-mg/kg dose, the overall response rate was 75%, and the median time to first response was 1.5 months (range, 0.9-5.1). The median duration of response — measured from first response to progression, death, or switch to a new systemic therapy for chronic GVHD — was 1.9 months. 

In those who responded to the therapy, there were no deaths or new therapies required in 60% of patients.

The most common adverse reactions, occurring in 15% or more patients, included increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, nausea, headache, diarrhea, cough, pyrexia, and dyspnea. 

In the AGAVE-201 trial results, researchers noted that drug discontinuation from treatment-emergent adverse events occurred in 6% of patients in the 0.3-mg/kg cohort, in 22% in the 1-mg/kg cohort, and in 18% in the 3-mg/kg cohort. Fatal treatment-emergent adverse events occurred in 1.3% of patients in the 0.3-mg/kg cohort. 

“Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” lead study author Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg, Germany, said in a company press release. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pretreated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

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

The US Food and Drug Administration (FDA) has approved axatilimab (Niktimvo, Incyte Corporation and Syndax) for the treatment of adult and pediatric patients with chronic graft versus host disease (GVHD) who have not responded to at least two prior lines of systemic therapy and who weigh ≥ 40 kg.

Chronic GVHD is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation that develops in about 50% of transplant recipients.

The first-in-class treatment for chronic GVHD is a monoclonal antibody that targets the colony-stimulating factor 1 (CSF-1) receptor. Approval for axatilimab followed priority review of Incyte’s Biologic License Application and was based on findings from the open-label phase 2 AGAVE-201 trial. 

Study participants had chronic GVHD after allogeneic hematopoietic stem cell transplantation and had failed to respond to at least two prior lines of systemic therapy (median, four lines of therapy). Prior therapies included ruxolitinib, belumosudil, and ibrutinib in 74%, 23%, and 31% of patients, respectively. Overall, 239 patients were enrolled at 121 study sites and were randomly assigned 1:1:1 to three doses.

The FDA recommended dose of axatilimab is 0.3 mg/kg (to a maximum of 35 mg) as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. Other doses tested in the AGAVE-201 trial were 1 mg/kg every 2 weeks and 3 mg/kg every 4 weeks. 

The trial measured overall response rate over the first six cycles (24 weeks). In the 79 patients who received the recommended 0.3-mg/kg dose, the overall response rate was 75%, and the median time to first response was 1.5 months (range, 0.9-5.1). The median duration of response — measured from first response to progression, death, or switch to a new systemic therapy for chronic GVHD — was 1.9 months. 

In those who responded to the therapy, there were no deaths or new therapies required in 60% of patients.

The most common adverse reactions, occurring in 15% or more patients, included increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, nausea, headache, diarrhea, cough, pyrexia, and dyspnea. 

In the AGAVE-201 trial results, researchers noted that drug discontinuation from treatment-emergent adverse events occurred in 6% of patients in the 0.3-mg/kg cohort, in 22% in the 1-mg/kg cohort, and in 18% in the 3-mg/kg cohort. Fatal treatment-emergent adverse events occurred in 1.3% of patients in the 0.3-mg/kg cohort. 

“Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” lead study author Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg, Germany, said in a company press release. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pretreated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

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

The US Food and Drug Administration (FDA) has approved vorasidenib (Voranigo, Servier) for the treatment of certain isocitrate dehydrogenase (IDH)–mutant diffuse gliomas, marking the first approval of a targeted therapy for these types of brain tumors.

Specifically, the oral targeted inhibitor of IDH1 and IDH2 was approved for use after surgery in adults and children aged 12 years or older who have grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. According to the FDA, surgery includes biopsy, subtotal resection, or gross total resection. 

Mutations in IDH1 are present in around 80% of grade 2 gliomas, whereas IDH2 mutations are more infrequent, occurring in about 4%. 

Prior to the approval, which was based on progression-free survival (PFS) and safety findings from the pivotal phase 3 INDIGO trial, patients with this type of glioma had limited treatment options, said a Servier spokesperson.

The approval of vorasidenib marks “one of the biggest advances in low-grade glioma in more than two decades” and “will empower patients to take active control of their disease with a once-daily pill,” according to the spokesperson.

In the INDIGO trial, 331 patients were randomly assigned to receive 40 mg of vorasidenib once daily (n = 168) or placebo (n = 163). At a median follow-up of 14.2 months, the median PFS was more than twice as long among those who received vorasidenib vs placebo: 27.7 months vs 11.1 months, respectively (hazard ratio [HR] for disease progression or death, 0.39). The time to next intervention was also significantly longer with vorasidenib vs placebo (median not reached vs 17.8 months, respectively; HR, 0.26).

The 61% reduction in the risk for tumor progression or death observed in the trial represents “a significant sign of efficacy that has the potential to change the landscape in this disease,” first author Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York City, told this news organization in 2023, when presenting the findings at the 2023 American Society of Clinical Oncology conference. These findings were simultaneously published in The New England Journal of Medicine.

Glenn Lesser, MD, a discussant at the 2023 meeting, commented on the “striking” findings. The results are “statistically highly significant, and more importantly, they’re clinically very, very significant,” said Dr. Lesser, from Wake Forest Baptist Health in Winston-Salem, North Carolina.

Vorasidenib can also potentially delay the use of toxic chemotherapies and radiation for many years in patients with these tumors, Dr. Lesser added.

Adverse events of grade 3 or higher occurred in 22.8% of those who received vorasidenib and in 13.5% of those in the placebo group. Increased alanine aminotransferase levels of grade 3 or higher occurred in 9.6 vs 0% of patients in the groups, respectively.

The most common adverse reactions with vorasidenib, affecting at least 15% of treated patients, include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as decreased neutrophils. 

The recommended dose of vorasidenib for adults is 40 mg given orally once daily until disease progression or unacceptable toxicity. In children aged 12 or older, the recommended dose is 40 mg given orally once daily for those weighing ≥ 40 kg, and 20 mg given orally once daily for those weighing < 40 kg.

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

The US Food and Drug Administration (FDA) has approved vorasidenib (Voranigo, Servier) for the treatment of certain isocitrate dehydrogenase (IDH)–mutant diffuse gliomas, marking the first approval of a targeted therapy for these types of brain tumors.

Specifically, the oral targeted inhibitor of IDH1 and IDH2 was approved for use after surgery in adults and children aged 12 years or older who have grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. According to the FDA, surgery includes biopsy, subtotal resection, or gross total resection. 

Mutations in IDH1 are present in around 80% of grade 2 gliomas, whereas IDH2 mutations are more infrequent, occurring in about 4%. 

Prior to the approval, which was based on progression-free survival (PFS) and safety findings from the pivotal phase 3 INDIGO trial, patients with this type of glioma had limited treatment options, said a Servier spokesperson.

The approval of vorasidenib marks “one of the biggest advances in low-grade glioma in more than two decades” and “will empower patients to take active control of their disease with a once-daily pill,” according to the spokesperson.

In the INDIGO trial, 331 patients were randomly assigned to receive 40 mg of vorasidenib once daily (n = 168) or placebo (n = 163). At a median follow-up of 14.2 months, the median PFS was more than twice as long among those who received vorasidenib vs placebo: 27.7 months vs 11.1 months, respectively (hazard ratio [HR] for disease progression or death, 0.39). The time to next intervention was also significantly longer with vorasidenib vs placebo (median not reached vs 17.8 months, respectively; HR, 0.26).

The 61% reduction in the risk for tumor progression or death observed in the trial represents “a significant sign of efficacy that has the potential to change the landscape in this disease,” first author Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York City, told this news organization in 2023, when presenting the findings at the 2023 American Society of Clinical Oncology conference. These findings were simultaneously published in The New England Journal of Medicine.

Glenn Lesser, MD, a discussant at the 2023 meeting, commented on the “striking” findings. The results are “statistically highly significant, and more importantly, they’re clinically very, very significant,” said Dr. Lesser, from Wake Forest Baptist Health in Winston-Salem, North Carolina.

Vorasidenib can also potentially delay the use of toxic chemotherapies and radiation for many years in patients with these tumors, Dr. Lesser added.

Adverse events of grade 3 or higher occurred in 22.8% of those who received vorasidenib and in 13.5% of those in the placebo group. Increased alanine aminotransferase levels of grade 3 or higher occurred in 9.6 vs 0% of patients in the groups, respectively.

The most common adverse reactions with vorasidenib, affecting at least 15% of treated patients, include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as decreased neutrophils. 

The recommended dose of vorasidenib for adults is 40 mg given orally once daily until disease progression or unacceptable toxicity. In children aged 12 or older, the recommended dose is 40 mg given orally once daily for those weighing ≥ 40 kg, and 20 mg given orally once daily for those weighing < 40 kg.

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

The US Food and Drug Administration (FDA) has approved vorasidenib (Voranigo, Servier) for the treatment of certain isocitrate dehydrogenase (IDH)–mutant diffuse gliomas, marking the first approval of a targeted therapy for these types of brain tumors.

Specifically, the oral targeted inhibitor of IDH1 and IDH2 was approved for use after surgery in adults and children aged 12 years or older who have grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. According to the FDA, surgery includes biopsy, subtotal resection, or gross total resection. 

Mutations in IDH1 are present in around 80% of grade 2 gliomas, whereas IDH2 mutations are more infrequent, occurring in about 4%. 

Prior to the approval, which was based on progression-free survival (PFS) and safety findings from the pivotal phase 3 INDIGO trial, patients with this type of glioma had limited treatment options, said a Servier spokesperson.

The approval of vorasidenib marks “one of the biggest advances in low-grade glioma in more than two decades” and “will empower patients to take active control of their disease with a once-daily pill,” according to the spokesperson.

In the INDIGO trial, 331 patients were randomly assigned to receive 40 mg of vorasidenib once daily (n = 168) or placebo (n = 163). At a median follow-up of 14.2 months, the median PFS was more than twice as long among those who received vorasidenib vs placebo: 27.7 months vs 11.1 months, respectively (hazard ratio [HR] for disease progression or death, 0.39). The time to next intervention was also significantly longer with vorasidenib vs placebo (median not reached vs 17.8 months, respectively; HR, 0.26).

The 61% reduction in the risk for tumor progression or death observed in the trial represents “a significant sign of efficacy that has the potential to change the landscape in this disease,” first author Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York City, told this news organization in 2023, when presenting the findings at the 2023 American Society of Clinical Oncology conference. These findings were simultaneously published in The New England Journal of Medicine.

Glenn Lesser, MD, a discussant at the 2023 meeting, commented on the “striking” findings. The results are “statistically highly significant, and more importantly, they’re clinically very, very significant,” said Dr. Lesser, from Wake Forest Baptist Health in Winston-Salem, North Carolina.

Vorasidenib can also potentially delay the use of toxic chemotherapies and radiation for many years in patients with these tumors, Dr. Lesser added.

Adverse events of grade 3 or higher occurred in 22.8% of those who received vorasidenib and in 13.5% of those in the placebo group. Increased alanine aminotransferase levels of grade 3 or higher occurred in 9.6 vs 0% of patients in the groups, respectively.

The most common adverse reactions with vorasidenib, affecting at least 15% of treated patients, include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as decreased neutrophils. 

The recommended dose of vorasidenib for adults is 40 mg given orally once daily until disease progression or unacceptable toxicity. In children aged 12 or older, the recommended dose is 40 mg given orally once daily for those weighing ≥ 40 kg, and 20 mg given orally once daily for those weighing < 40 kg.

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

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

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

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

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

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

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

The US Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Research and Development LLC) in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma.

Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA. 

Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.

Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash. 

The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.

Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.

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

The US Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Research and Development LLC) in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma.

Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA. 

Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.

Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash. 

The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.

Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.

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

The US Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Research and Development LLC) in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma.

Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA. 

Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.

Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash. 

The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.

Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.

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

The Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Research and Development) in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma.

Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA. 

Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.

Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash. 

The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.

Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Research and Development) in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma.

Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA. 

Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.

Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash. 

The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.

Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Research and Development) in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma.

Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA. 

Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.

Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash. 

The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.

Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) recently approved two biosimilars to Soliris for the treatment of two rare diseases — paroxysmal nocturnal hemoglobinuria (PNH), a debilitating and potentially deadly blood disorder, and atypical hemolytic uremic syndrome.

The first, Bkemv (eculizumab-aeeb, Amgen), was approved in May, and the second, Epysqli (eculizumab-aagh, Samsung Bioepis), was approved on July 22.

Soliris (eculizumab, Alexion) is an intravenous agent indicated for the treatment of PNH and atypical hemolytic uremic syndrome, as well as generalized myasthenia gravis and neuromyelitis optical spectrum disorder.

Both Bkemv and Epysqli are monoclonal antibodies that bind to complement protein C5 and have been approved previously in Europe. Availability for Bkemv in the United States will be delayed until March 1, 2025, under a patent settlement agreement between Alexion and Amgen.

The FDA approval for Bkemv was based on findings from the double-blind, active-controlled, phase 3 DAHLIA study showing similar efficacy, safety, and immunogenicity to Soliris in adults with PNH. The agents reduce the loss of red blood cells and, thus, the need for blood transfusion in patients with PNH.

The DAHLIA study included 42 adults with PNH who had previously received Soliris for at least 6 months. These patients were then randomized to receive Soliris or Bkemv in one of two sequences delivered across two treatment periods. For study period 1 (weeks 1-53), patients were randomized to either 900 mg of intravenous (IV) Bkemv or Soliris every 14 days for 52 weeks, and for study period 2, the patients crossed over to the other treatment for 26 weeks.

Comparable efficacy was observed in both the parallel and crossover comparisons, with geometric mean values for trough total and unbound concentrations of Bkemv and Soliris similar between the treatment groups at all time points tested. Control of intravascular hemolysis was measured by lactate dehydrogenase at week 27 for the parallel comparison and by time-adjusted area under the effect curve of lactate dehydrogenase from weeks 13 to 27, from weeks 39 to 53, and from weeks 65 to 79 for the crossover comparison.

The approval for Epysqli was on the basis of phase 3 trial findings, in which 50 patients with PNH were randomized to Epysqli or Soliris through week 26, after which the treatment was switched and provided until week 50. The findings showed a mean difference in lactate dehydrogenase level at week 26 between Epysqli and Soliris was 34.48 U/L, which fell within the predefined equivalence margin. The ratio of time-adjusted area under the effect curve of lactate dehydrogenase between the two was 1.08 — also within the predefined equivalence margin — indicating bioequivalence between the biosimilar and reference product.

Similar to Soliris, the prescribing information for Bkemv and Epysqli includes a boxed warning associated with an increased risk for serious meningococcal infections. Because of this risk, both biosimilars are only available under a Risk Evaluation and Mitigation Strategy program that prescribers are required to enroll in.

According to drugs.com, Soliris (10 mg/mL) IV solution comes to about $6878 for a supply of 30 milliliters; cost information for the biosimilars is not available yet.

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

The Food and Drug Administration (FDA) recently approved two biosimilars to Soliris for the treatment of two rare diseases — paroxysmal nocturnal hemoglobinuria (PNH), a debilitating and potentially deadly blood disorder, and atypical hemolytic uremic syndrome.

The first, Bkemv (eculizumab-aeeb, Amgen), was approved in May, and the second, Epysqli (eculizumab-aagh, Samsung Bioepis), was approved on July 22.

Soliris (eculizumab, Alexion) is an intravenous agent indicated for the treatment of PNH and atypical hemolytic uremic syndrome, as well as generalized myasthenia gravis and neuromyelitis optical spectrum disorder.

Both Bkemv and Epysqli are monoclonal antibodies that bind to complement protein C5 and have been approved previously in Europe. Availability for Bkemv in the United States will be delayed until March 1, 2025, under a patent settlement agreement between Alexion and Amgen.

The FDA approval for Bkemv was based on findings from the double-blind, active-controlled, phase 3 DAHLIA study showing similar efficacy, safety, and immunogenicity to Soliris in adults with PNH. The agents reduce the loss of red blood cells and, thus, the need for blood transfusion in patients with PNH.

The DAHLIA study included 42 adults with PNH who had previously received Soliris for at least 6 months. These patients were then randomized to receive Soliris or Bkemv in one of two sequences delivered across two treatment periods. For study period 1 (weeks 1-53), patients were randomized to either 900 mg of intravenous (IV) Bkemv or Soliris every 14 days for 52 weeks, and for study period 2, the patients crossed over to the other treatment for 26 weeks.

Comparable efficacy was observed in both the parallel and crossover comparisons, with geometric mean values for trough total and unbound concentrations of Bkemv and Soliris similar between the treatment groups at all time points tested. Control of intravascular hemolysis was measured by lactate dehydrogenase at week 27 for the parallel comparison and by time-adjusted area under the effect curve of lactate dehydrogenase from weeks 13 to 27, from weeks 39 to 53, and from weeks 65 to 79 for the crossover comparison.

The approval for Epysqli was on the basis of phase 3 trial findings, in which 50 patients with PNH were randomized to Epysqli or Soliris through week 26, after which the treatment was switched and provided until week 50. The findings showed a mean difference in lactate dehydrogenase level at week 26 between Epysqli and Soliris was 34.48 U/L, which fell within the predefined equivalence margin. The ratio of time-adjusted area under the effect curve of lactate dehydrogenase between the two was 1.08 — also within the predefined equivalence margin — indicating bioequivalence between the biosimilar and reference product.

Similar to Soliris, the prescribing information for Bkemv and Epysqli includes a boxed warning associated with an increased risk for serious meningococcal infections. Because of this risk, both biosimilars are only available under a Risk Evaluation and Mitigation Strategy program that prescribers are required to enroll in.

According to drugs.com, Soliris (10 mg/mL) IV solution comes to about $6878 for a supply of 30 milliliters; cost information for the biosimilars is not available yet.

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

The Food and Drug Administration (FDA) recently approved two biosimilars to Soliris for the treatment of two rare diseases — paroxysmal nocturnal hemoglobinuria (PNH), a debilitating and potentially deadly blood disorder, and atypical hemolytic uremic syndrome.

The first, Bkemv (eculizumab-aeeb, Amgen), was approved in May, and the second, Epysqli (eculizumab-aagh, Samsung Bioepis), was approved on July 22.

Soliris (eculizumab, Alexion) is an intravenous agent indicated for the treatment of PNH and atypical hemolytic uremic syndrome, as well as generalized myasthenia gravis and neuromyelitis optical spectrum disorder.

Both Bkemv and Epysqli are monoclonal antibodies that bind to complement protein C5 and have been approved previously in Europe. Availability for Bkemv in the United States will be delayed until March 1, 2025, under a patent settlement agreement between Alexion and Amgen.

The FDA approval for Bkemv was based on findings from the double-blind, active-controlled, phase 3 DAHLIA study showing similar efficacy, safety, and immunogenicity to Soliris in adults with PNH. The agents reduce the loss of red blood cells and, thus, the need for blood transfusion in patients with PNH.

The DAHLIA study included 42 adults with PNH who had previously received Soliris for at least 6 months. These patients were then randomized to receive Soliris or Bkemv in one of two sequences delivered across two treatment periods. For study period 1 (weeks 1-53), patients were randomized to either 900 mg of intravenous (IV) Bkemv or Soliris every 14 days for 52 weeks, and for study period 2, the patients crossed over to the other treatment for 26 weeks.

Comparable efficacy was observed in both the parallel and crossover comparisons, with geometric mean values for trough total and unbound concentrations of Bkemv and Soliris similar between the treatment groups at all time points tested. Control of intravascular hemolysis was measured by lactate dehydrogenase at week 27 for the parallel comparison and by time-adjusted area under the effect curve of lactate dehydrogenase from weeks 13 to 27, from weeks 39 to 53, and from weeks 65 to 79 for the crossover comparison.

The approval for Epysqli was on the basis of phase 3 trial findings, in which 50 patients with PNH were randomized to Epysqli or Soliris through week 26, after which the treatment was switched and provided until week 50. The findings showed a mean difference in lactate dehydrogenase level at week 26 between Epysqli and Soliris was 34.48 U/L, which fell within the predefined equivalence margin. The ratio of time-adjusted area under the effect curve of lactate dehydrogenase between the two was 1.08 — also within the predefined equivalence margin — indicating bioequivalence between the biosimilar and reference product.

Similar to Soliris, the prescribing information for Bkemv and Epysqli includes a boxed warning associated with an increased risk for serious meningococcal infections. Because of this risk, both biosimilars are only available under a Risk Evaluation and Mitigation Strategy program that prescribers are required to enroll in.

According to drugs.com, Soliris (10 mg/mL) IV solution comes to about $6878 for a supply of 30 milliliters; cost information for the biosimilars is not available yet.

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

CHICAGO — An abbreviated course of azacitidine for 7 days plus venetoclax for 7 days showed similar efficacy to a standard hypomethylating agent plus venetoclax doublets in older and unfit patients with newly diagnosed acute myeloid leukemia (AML) in a multicenter retrospective analysis.

However, the azacitidine plus venetoclax therapy — the “7+7” regimen — was associated with lower platelet transfusion requirements and lower 8-week mortality, suggesting the regimen might be preferable in certain patient populations, Alexandre Bazinet, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The composite complete remission (CRc) rate, including complete remission with or without complete count recovery, was identical at 72% among 82 patients treated with the 7+7 regimen and 166 treated with standard therapy, and the complete remission (CR) rate was 57% and 55%, respectively, Dr. Bazinet said.

The median number of cycles to first response was one in both groups, but 42% of responders in the 7+7 group required more than one cycle to achieve their first response, compared with just 1% of those in the standard therapy group, he noted, adding that the median number of cycles to achieve best response was two in the 7+7 group and one in the standard therapy group.

The mortality rate at 4 weeks was similar in the groups (2% vs 5% for 7+7 vs standard therapy), but at 8 weeks, the mortality rate was significantly higher in the standard therapy group (6% vs 16%, respectively). Median overall survival (OS) was 11.2 months versus 10.3 months, and median 2-year survival was 27.7% versus 33.6% in the groups, respectively.

Event-free survival was 6.5 versus 7.4 months, and 2-year event-free survival was 24.5% versus 27.0%, respectively.

Of note, fewer patients in the 7+7 group required platelet transfusions during cycle 1 (62% vs 77%) and the cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar in the two treatment groups, Dr. Bazinet said.

Study participants were 82 adults from seven centers in France who received the 7+7 regimen, and 166 adults from MD Anderson who received standard therapy with a hypomethylating agent plus venetoclax doublets given for 21-28 days during induction. Preliminary data on the 7+7 regimen in patients from the French centers were reported previously and “suggested preserved efficacy with potentially less toxicity,” he noted.

“A hypomethylating agent plus venetoclax doublets are standard-of-care in patients with AML who are older or ineligible for chemotherapy due to comorbidities,” Dr. Bazinet explained, adding that although the venetoclax label calls for 28 days of drug per cycle, shorter courses of 14 to 21 days are commonly used.

These findings are limited by the retrospective study design and by small patient numbers in many subgroups, he said.

“In addition, the cohorts were heterogeneous, consisting of patients treated with a variety of different regimens and across multiple centers and countries. The distribution of FLT3-ITD and NRAS/KRAS mutations differed significantly between cohorts,” he explained, also noting that prophylactic azole use differed across the cohort. “Furthermore, analysis of the toxicity results was also limited by likely differing transfusion polices in different centers.”

Overall, however, the findings suggest that reducing the duration of venetoclax is safe and results in similar CRc rates, although responses may be faster with standard dosing, he said, adding that “7+7 is potentially less toxic and is attractive in patients who are more frail or at risk for complications.”

“Our data support further study of shorter venetoclax duration, within emerging triplet regimens in patients with intermediate or low predictive benefit to mitigate toxicity,” he concluded.

Dr. Bazinet reported having no disclosures.

CHICAGO — An abbreviated course of azacitidine for 7 days plus venetoclax for 7 days showed similar efficacy to a standard hypomethylating agent plus venetoclax doublets in older and unfit patients with newly diagnosed acute myeloid leukemia (AML) in a multicenter retrospective analysis.

However, the azacitidine plus venetoclax therapy — the “7+7” regimen — was associated with lower platelet transfusion requirements and lower 8-week mortality, suggesting the regimen might be preferable in certain patient populations, Alexandre Bazinet, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The composite complete remission (CRc) rate, including complete remission with or without complete count recovery, was identical at 72% among 82 patients treated with the 7+7 regimen and 166 treated with standard therapy, and the complete remission (CR) rate was 57% and 55%, respectively, Dr. Bazinet said.

The median number of cycles to first response was one in both groups, but 42% of responders in the 7+7 group required more than one cycle to achieve their first response, compared with just 1% of those in the standard therapy group, he noted, adding that the median number of cycles to achieve best response was two in the 7+7 group and one in the standard therapy group.

The mortality rate at 4 weeks was similar in the groups (2% vs 5% for 7+7 vs standard therapy), but at 8 weeks, the mortality rate was significantly higher in the standard therapy group (6% vs 16%, respectively). Median overall survival (OS) was 11.2 months versus 10.3 months, and median 2-year survival was 27.7% versus 33.6% in the groups, respectively.

Event-free survival was 6.5 versus 7.4 months, and 2-year event-free survival was 24.5% versus 27.0%, respectively.

Of note, fewer patients in the 7+7 group required platelet transfusions during cycle 1 (62% vs 77%) and the cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar in the two treatment groups, Dr. Bazinet said.

Study participants were 82 adults from seven centers in France who received the 7+7 regimen, and 166 adults from MD Anderson who received standard therapy with a hypomethylating agent plus venetoclax doublets given for 21-28 days during induction. Preliminary data on the 7+7 regimen in patients from the French centers were reported previously and “suggested preserved efficacy with potentially less toxicity,” he noted.

“A hypomethylating agent plus venetoclax doublets are standard-of-care in patients with AML who are older or ineligible for chemotherapy due to comorbidities,” Dr. Bazinet explained, adding that although the venetoclax label calls for 28 days of drug per cycle, shorter courses of 14 to 21 days are commonly used.

These findings are limited by the retrospective study design and by small patient numbers in many subgroups, he said.

“In addition, the cohorts were heterogeneous, consisting of patients treated with a variety of different regimens and across multiple centers and countries. The distribution of FLT3-ITD and NRAS/KRAS mutations differed significantly between cohorts,” he explained, also noting that prophylactic azole use differed across the cohort. “Furthermore, analysis of the toxicity results was also limited by likely differing transfusion polices in different centers.”

Overall, however, the findings suggest that reducing the duration of venetoclax is safe and results in similar CRc rates, although responses may be faster with standard dosing, he said, adding that “7+7 is potentially less toxic and is attractive in patients who are more frail or at risk for complications.”

“Our data support further study of shorter venetoclax duration, within emerging triplet regimens in patients with intermediate or low predictive benefit to mitigate toxicity,” he concluded.

Dr. Bazinet reported having no disclosures.

CHICAGO — An abbreviated course of azacitidine for 7 days plus venetoclax for 7 days showed similar efficacy to a standard hypomethylating agent plus venetoclax doublets in older and unfit patients with newly diagnosed acute myeloid leukemia (AML) in a multicenter retrospective analysis.

However, the azacitidine plus venetoclax therapy — the “7+7” regimen — was associated with lower platelet transfusion requirements and lower 8-week mortality, suggesting the regimen might be preferable in certain patient populations, Alexandre Bazinet, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The composite complete remission (CRc) rate, including complete remission with or without complete count recovery, was identical at 72% among 82 patients treated with the 7+7 regimen and 166 treated with standard therapy, and the complete remission (CR) rate was 57% and 55%, respectively, Dr. Bazinet said.

The median number of cycles to first response was one in both groups, but 42% of responders in the 7+7 group required more than one cycle to achieve their first response, compared with just 1% of those in the standard therapy group, he noted, adding that the median number of cycles to achieve best response was two in the 7+7 group and one in the standard therapy group.

The mortality rate at 4 weeks was similar in the groups (2% vs 5% for 7+7 vs standard therapy), but at 8 weeks, the mortality rate was significantly higher in the standard therapy group (6% vs 16%, respectively). Median overall survival (OS) was 11.2 months versus 10.3 months, and median 2-year survival was 27.7% versus 33.6% in the groups, respectively.

Event-free survival was 6.5 versus 7.4 months, and 2-year event-free survival was 24.5% versus 27.0%, respectively.

Of note, fewer patients in the 7+7 group required platelet transfusions during cycle 1 (62% vs 77%) and the cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar in the two treatment groups, Dr. Bazinet said.

Study participants were 82 adults from seven centers in France who received the 7+7 regimen, and 166 adults from MD Anderson who received standard therapy with a hypomethylating agent plus venetoclax doublets given for 21-28 days during induction. Preliminary data on the 7+7 regimen in patients from the French centers were reported previously and “suggested preserved efficacy with potentially less toxicity,” he noted.

“A hypomethylating agent plus venetoclax doublets are standard-of-care in patients with AML who are older or ineligible for chemotherapy due to comorbidities,” Dr. Bazinet explained, adding that although the venetoclax label calls for 28 days of drug per cycle, shorter courses of 14 to 21 days are commonly used.

These findings are limited by the retrospective study design and by small patient numbers in many subgroups, he said.

“In addition, the cohorts were heterogeneous, consisting of patients treated with a variety of different regimens and across multiple centers and countries. The distribution of FLT3-ITD and NRAS/KRAS mutations differed significantly between cohorts,” he explained, also noting that prophylactic azole use differed across the cohort. “Furthermore, analysis of the toxicity results was also limited by likely differing transfusion polices in different centers.”

Overall, however, the findings suggest that reducing the duration of venetoclax is safe and results in similar CRc rates, although responses may be faster with standard dosing, he said, adding that “7+7 is potentially less toxic and is attractive in patients who are more frail or at risk for complications.”

“Our data support further study of shorter venetoclax duration, within emerging triplet regimens in patients with intermediate or low predictive benefit to mitigate toxicity,” he concluded.

Dr. Bazinet reported having no disclosures.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.