Hematology News

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved imetelstat (Rytelo, Geron Corporation) for certain patients with relapsed or refractory low- to intermediate-risk myelodysplastic syndromes (MDS).

Specifically, the first-in-class oligonucleotide telomerase inhibitor, which received orphan drug designation, is indicated for adults with MDS who have transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks and who have not responded to erythropoiesis-stimulating agents or who have lost response to or are not eligible for erythropoiesis-stimulating agents, according to an FDA press release.

“For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of RYTELO potentially practice changing for us,” co-investigator Rami Komrokji, MD, of Moffitt Cancer Center, Tampa, Florida, said in the Geron Corporation’s announcement of the approval.

Approval was based on efficacy and safety findings from the randomized, placebo-controlled, phase 3 IMerge trial, which found significantly improved red blood cell transfusion independence with treatment vs with placebo.

Overall, 178 patients were randomly assigned to the imetelstat arm (n = 118) and the placebo arm (n = 60). The median follow-up was 19.5 months in the treatment arm and 17.5 months in the placebo arm.

Patients received infusions of either 7.1 mg/kg of imetelstat or placebo in 28-day cycles until disease progression or unacceptable toxicity. All patients received supportive care, including red blood cell transfusions.

The rate of 8-week-or-greater red blood cell transfusion independence was 39.8% in the imetelstat vs 15% placebo arm. The rate of 24-week-or-greater red blood cell transfusion independence was 28% in the treatment arm vs 3.3% in the placebo arm.

An exploratory analysis among patients who achieved at least 8 weeks of red blood cell transfusion independence revealed that median increases in hemoglobin were 3.6 g/dL in the treatment group vs 0.8 g/dL in the placebo group.

Adverse reactions, occurring in at least 10% of patients and in at least 5% more patients in the treatment arm than in the placebo arm, included decreased platelets, white blood cells, and neutrophils; increased aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase; and fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19, and headache.

The recommended imetelstat dose is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 28 days, according to the full prescribing information. 

“What is exciting about RYTELO is the totality of the clinical benefit across [lower risk] MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias,” Dr. Komrokji stated. The treatment goal for patients with this condition “is transfusion-independence and before today, this wasn’t possible for many patients.”
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved imetelstat (Rytelo, Geron Corporation) for certain patients with relapsed or refractory low- to intermediate-risk myelodysplastic syndromes (MDS).

Specifically, the first-in-class oligonucleotide telomerase inhibitor, which received orphan drug designation, is indicated for adults with MDS who have transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks and who have not responded to erythropoiesis-stimulating agents or who have lost response to or are not eligible for erythropoiesis-stimulating agents, according to an FDA press release.

“For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of RYTELO potentially practice changing for us,” co-investigator Rami Komrokji, MD, of Moffitt Cancer Center, Tampa, Florida, said in the Geron Corporation’s announcement of the approval.

Approval was based on efficacy and safety findings from the randomized, placebo-controlled, phase 3 IMerge trial, which found significantly improved red blood cell transfusion independence with treatment vs with placebo.

Overall, 178 patients were randomly assigned to the imetelstat arm (n = 118) and the placebo arm (n = 60). The median follow-up was 19.5 months in the treatment arm and 17.5 months in the placebo arm.

Patients received infusions of either 7.1 mg/kg of imetelstat or placebo in 28-day cycles until disease progression or unacceptable toxicity. All patients received supportive care, including red blood cell transfusions.

The rate of 8-week-or-greater red blood cell transfusion independence was 39.8% in the imetelstat vs 15% placebo arm. The rate of 24-week-or-greater red blood cell transfusion independence was 28% in the treatment arm vs 3.3% in the placebo arm.

An exploratory analysis among patients who achieved at least 8 weeks of red blood cell transfusion independence revealed that median increases in hemoglobin were 3.6 g/dL in the treatment group vs 0.8 g/dL in the placebo group.

Adverse reactions, occurring in at least 10% of patients and in at least 5% more patients in the treatment arm than in the placebo arm, included decreased platelets, white blood cells, and neutrophils; increased aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase; and fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19, and headache.

The recommended imetelstat dose is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 28 days, according to the full prescribing information. 

“What is exciting about RYTELO is the totality of the clinical benefit across [lower risk] MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias,” Dr. Komrokji stated. The treatment goal for patients with this condition “is transfusion-independence and before today, this wasn’t possible for many patients.”
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved imetelstat (Rytelo, Geron Corporation) for certain patients with relapsed or refractory low- to intermediate-risk myelodysplastic syndromes (MDS).

Specifically, the first-in-class oligonucleotide telomerase inhibitor, which received orphan drug designation, is indicated for adults with MDS who have transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks and who have not responded to erythropoiesis-stimulating agents or who have lost response to or are not eligible for erythropoiesis-stimulating agents, according to an FDA press release.

“For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of RYTELO potentially practice changing for us,” co-investigator Rami Komrokji, MD, of Moffitt Cancer Center, Tampa, Florida, said in the Geron Corporation’s announcement of the approval.

Approval was based on efficacy and safety findings from the randomized, placebo-controlled, phase 3 IMerge trial, which found significantly improved red blood cell transfusion independence with treatment vs with placebo.

Overall, 178 patients were randomly assigned to the imetelstat arm (n = 118) and the placebo arm (n = 60). The median follow-up was 19.5 months in the treatment arm and 17.5 months in the placebo arm.

Patients received infusions of either 7.1 mg/kg of imetelstat or placebo in 28-day cycles until disease progression or unacceptable toxicity. All patients received supportive care, including red blood cell transfusions.

The rate of 8-week-or-greater red blood cell transfusion independence was 39.8% in the imetelstat vs 15% placebo arm. The rate of 24-week-or-greater red blood cell transfusion independence was 28% in the treatment arm vs 3.3% in the placebo arm.

An exploratory analysis among patients who achieved at least 8 weeks of red blood cell transfusion independence revealed that median increases in hemoglobin were 3.6 g/dL in the treatment group vs 0.8 g/dL in the placebo group.

Adverse reactions, occurring in at least 10% of patients and in at least 5% more patients in the treatment arm than in the placebo arm, included decreased platelets, white blood cells, and neutrophils; increased aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase; and fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19, and headache.

The recommended imetelstat dose is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 28 days, according to the full prescribing information. 

“What is exciting about RYTELO is the totality of the clinical benefit across [lower risk] MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias,” Dr. Komrokji stated. The treatment goal for patients with this condition “is transfusion-independence and before today, this wasn’t possible for many patients.”
 

A version of this article appeared on Medscape.com.

Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.

These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.

“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.

The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.

Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
 

The Study

HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.

In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).

Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:

• 1957 (3.12%) according to HEIRS
• 4659 (7.43%) according to WHO
• 9611 (15.33%) according to IDE

Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.

In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.

Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.

An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”

“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”

The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.

Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.

These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.

“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.

The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.

Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
 

The Study

HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.

In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).

Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:

• 1957 (3.12%) according to HEIRS
• 4659 (7.43%) according to WHO
• 9611 (15.33%) according to IDE

Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.

In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.

Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.

An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”

“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”

The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.

Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.

These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.

“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.

The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.

Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
 

The Study

HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.

In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).

Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:

• 1957 (3.12%) according to HEIRS
• 4659 (7.43%) according to WHO
• 9611 (15.33%) according to IDE

Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.

In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.

Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.

An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”

“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”

The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In the common challenge of patients with relapsed multiple myeloma who are refractory to lenalidomide after receiving frontline treatment with the drug, treatment with the first-in-class, antibody-drug conjugate belantamab mafodotin, along with pomalidomide plus dexamethasone (pom-dex), shows significant improvement in durability and progression-free survival (PFS) over the standard of care approach.

“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.

The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).

The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).

The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.

The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.

While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.

Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.

In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.

Discontinuation rates for fatal or AEs of any cause were similar in both arms.

The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).

The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.

As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.

The AEs resulted in treatment discontinuation for 9% of patients.

The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.

“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.

Previous FDA Approval Withdrawn

Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).

However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.

Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”

While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”

Antibody-Drug Conjugates: Less is More?

The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”

In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).

In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”

He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”

“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.

“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.

That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”

And “less ocular toxicity with similar efficacy are big wins,” he added.

“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”

Other Therapies

In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.

Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.

While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.

“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.

The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.

The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.

In the common challenge of patients with relapsed multiple myeloma who are refractory to lenalidomide after receiving frontline treatment with the drug, treatment with the first-in-class, antibody-drug conjugate belantamab mafodotin, along with pomalidomide plus dexamethasone (pom-dex), shows significant improvement in durability and progression-free survival (PFS) over the standard of care approach.

“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.

The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).

The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).

The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.

The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.

While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.

Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.

In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.

Discontinuation rates for fatal or AEs of any cause were similar in both arms.

The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).

The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.

As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.

The AEs resulted in treatment discontinuation for 9% of patients.

The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.

“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.

Previous FDA Approval Withdrawn

Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).

However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.

Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”

While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”

Antibody-Drug Conjugates: Less is More?

The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”

In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).

In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”

He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”

“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.

“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.

That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”

And “less ocular toxicity with similar efficacy are big wins,” he added.

“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”

Other Therapies

In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.

Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.

While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.

“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.

The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.

The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.

In the common challenge of patients with relapsed multiple myeloma who are refractory to lenalidomide after receiving frontline treatment with the drug, treatment with the first-in-class, antibody-drug conjugate belantamab mafodotin, along with pomalidomide plus dexamethasone (pom-dex), shows significant improvement in durability and progression-free survival (PFS) over the standard of care approach.

“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.

The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).

The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).

The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.

The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.

While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.

Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.

In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.

Discontinuation rates for fatal or AEs of any cause were similar in both arms.

The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).

The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.

As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.

The AEs resulted in treatment discontinuation for 9% of patients.

The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.

“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.

Previous FDA Approval Withdrawn

Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).

However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.

Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”

While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”

Antibody-Drug Conjugates: Less is More?

The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”

In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).

In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”

He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”

“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.

“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.

That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”

And “less ocular toxicity with similar efficacy are big wins,” he added.

“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”

Other Therapies

In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.

Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.

While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.

“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.

The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.

The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

Asciminib, a first-in-class tyrosine kinase inhibitor (TKI), shows efficacy and significantly improved tolerability compared with standard of care TKIs as a frontline treatment of newly diagnosed chronic myeloid leukemia (CML), primary results from the pivotal ASC4FIRST trial show.

“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.

The study was published concurrently in The New England Journal of Medicine.

While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.

Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.

Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.

The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.

For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.

The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.

In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.

Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.

The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.

For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).

In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).

The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.

Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.

In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.

Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.

Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).

The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.

In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.

Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.

Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.

“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.

“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.

“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.

“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
 

Impressive Results; Financial Toxicity Concerns

In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.

“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”

He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”

“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”

Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.

“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.

Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”

Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”

Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.

Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.

“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.

“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.

The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.

Asciminib, a first-in-class tyrosine kinase inhibitor (TKI), shows efficacy and significantly improved tolerability compared with standard of care TKIs as a frontline treatment of newly diagnosed chronic myeloid leukemia (CML), primary results from the pivotal ASC4FIRST trial show.

“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.

The study was published concurrently in The New England Journal of Medicine.

While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.

Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.

Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.

The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.

For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.

The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.

In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.

Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.

The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.

For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).

In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).

The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.

Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.

In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.

Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.

Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).

The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.

In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.

Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.

Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.

“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.

“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.

“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.

“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
 

Impressive Results; Financial Toxicity Concerns

In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.

“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”

He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”

“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”

Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.

“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.

Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”

Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”

Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.

Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.

“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.

“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.

The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.

Asciminib, a first-in-class tyrosine kinase inhibitor (TKI), shows efficacy and significantly improved tolerability compared with standard of care TKIs as a frontline treatment of newly diagnosed chronic myeloid leukemia (CML), primary results from the pivotal ASC4FIRST trial show.

“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.

The study was published concurrently in The New England Journal of Medicine.

While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.

Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.

Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.

The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.

For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.

The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.

In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.

Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.

The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.

For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).

In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).

The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.

Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.

In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.

Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.

Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).

The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.

In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.

Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.

Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.

“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.

“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.

“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.

“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
 

Impressive Results; Financial Toxicity Concerns

In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.

“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”

He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”

“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”

Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.

“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.

Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”

Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”

Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.

Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.

“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.

“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.

The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .