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Imlunestrant Shows PFS Benefit in Advanced Breast Cancer
according to recent findings from the EMBER-3 trial.
This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.
Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”
The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.
However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.
First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.
Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.
The oral SERD imlunestrant is one such candidate.
The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.
About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.
Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.
When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.
Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.
The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).
Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.
All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.
The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.
EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.
A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.
Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.
She was also concerned about the use of monotherapy in the standard care arm.
“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.
Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.
Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
A version of this article appeared on Medscape.com.
according to recent findings from the EMBER-3 trial.
This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.
Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”
The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.
However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.
First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.
Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.
The oral SERD imlunestrant is one such candidate.
The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.
About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.
Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.
When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.
Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.
The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).
Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.
All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.
The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.
EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.
A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.
Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.
She was also concerned about the use of monotherapy in the standard care arm.
“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.
Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.
Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
A version of this article appeared on Medscape.com.
according to recent findings from the EMBER-3 trial.
This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.
Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”
The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.
However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.
First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.
Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.
The oral SERD imlunestrant is one such candidate.
The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.
About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.
Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.
When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.
Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.
The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).
Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.
All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.
The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.
EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.
A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.
Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.
She was also concerned about the use of monotherapy in the standard care arm.
“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.
Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.
Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
A version of this article appeared on Medscape.com.
FROM SABCS 2024
Smoldering MM: Big Prevention Benefits With Daratumumab?
Among 390 patients with SMM (194 assigned to daratumumab and 196 to active monitoring), progression to active MM or death over a follow-up of 65.2 (0-76.6) months was 51% lower in the daratumumab group vs active monitoring (34.5% vs 50.5%, hazard ratio [HR], 0.49; 95% CI, 0.36-0.67; P < .0001), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting and in a simultaneous publication in the New England Journal of Medicine.
Rahul Banerjee, MD, an assistant professor with the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, who wasn’t involved with the research, said the study “is a big deal, and I suspect this will ultimately lead to an FDA [Food and Drug Administration] approval for daratumumab in this setting. If using daratumumab up-front can prevent further myeloma and therefore make patients live longer, this would be immediately adopted at many practices.”
As study first author Meletios Athanasios Dimopoulos, MD, of National and Kapodistrian University of Athens and Alexandra General Hospital in Greece, noted at a news briefing, SMM is common, affecting 0.5% of the population aged over 40, per a 2023 Iceland study.
“Standard practice is close follow-up without immediate intervention. However, this oftentimes ends in organ tissue damage, and hypercalcemia, bone lesions, renal impairment, and anemia,” Dimopoulos said.
According to him, researchers launched the AQUILA study in light of indications that daratumumab may benefit patients with intermediate- and high-risk SMM.
For the study, researchers recruited patients from 2017 to 2019 in 23 countries with confirmed high-risk SMM for ≤ 5 years (median age, 64 [31-86] years; 47%-49% men; 83% White).
In the daratumumab group, the drug was administered in 28-day cycles until cycle 39, 36 months, or disease progression, whichever came first (median treatment duration, 38 months [35 months]).
At 5 years, progression-free survival (PFS) — the primary endpoint — was 63.1% (daratumumab) and 40.8% (active monitoring). Researchers estimated 60-month PFS rates at 63.1% and 40.8%, respectively, and overall response rates were 63.4% vs 2.0% (P < .0001), respectively.
The 60-month overall survival rates were 93.0% and 86.9% (HR, 0.52; 95% CI, 0.27-0.98) with 15 deaths in the daratumumab and 26 in the active monitoring group.
“During the follow-up period, there was continuous improvement in favor of the daratumumab arm,” Dimopoulos said. “Even after treatment was discontinued at 3 years, or even at 5 or 6 years, there was a continuous benefit from treatment with daratumumab.”
By clinical cutoff in May 2024, 65% of patients taking daratumumab had finished 39 cycles/3 years of treatment vs 40.8% in the active monitoring group. Progressive disease was the most common reason that patients stopped treatment (21.8% and 41.8% of patients in the groups, respectively).
Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 40.4% (daratumumab) and 30.1% (active monitoring) of patients. The most common was hypertension (5.7% and 4.6%, respectively).
In the daratumumab group, 5.7% discontinued therapy because of TEAEs, which the researchers described as a “low” number, and fatal TEAEs were similar in both groups (1.0% and 2.0%, respectively).
Banerjee said that “one theoretical risk of using daratumumab monotherapy to treat perceived high-risk SMM is that if the patient actually has active multiple myeloma, you are undertreating them. For anyone with HR-SMM, active multiple myeloma must be completely ruled out. I always insist on both a PET-CT and a whole-body MRI to evaluate the bone marrow comprehensively.”
For now, Banerjee said, clinicians should wait for the US Food and Drug Administration approval before prescribing daratumumab for high-risk SMM.
Are there alternatives to reduce the risk for SMM turning into MM? “Generally, I advise close observation in most cases, but we do have clinical trials in this space,” Banerjee said. “Technically, it is possible to consider lenalidomide monotherapy in SMM based on the results of a large phase 3 study. But lenalidomide is expensive and has many side effects. Insurance companies often won’t cover it fully, and patients almost always have at least one side effect.”
Also, he added, “only half of patients saw their high-risk SMM disease burden drop. Lenalidomide also has a clear link to rare, delayed toxicities such as second primary malignancies, which makes us nervous.”
Janssen Pharmaceuticals, the maker of daratumumab, funded the study. Dimopoulos disclosed ties with Sanofi, Regeneron, Menarini, Takeda, GSK, BMS, Janssen Pharmaceuticals, BeiGene, Swixx, AstraZeneca, and Amgen. Banerjee disclosed ties with AbbVie, Adaptive, BMS, Caribou, Genentech/Roche, GSK, Karyopharm Therapeutics, Legend, Johnson & Johnson, Novartis, Pack, Pfizer, Prothena, Sanofi Pasteur, and SparkCures. Some other authors reported various and multiple disclosures, including ties with Janssen Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Among 390 patients with SMM (194 assigned to daratumumab and 196 to active monitoring), progression to active MM or death over a follow-up of 65.2 (0-76.6) months was 51% lower in the daratumumab group vs active monitoring (34.5% vs 50.5%, hazard ratio [HR], 0.49; 95% CI, 0.36-0.67; P < .0001), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting and in a simultaneous publication in the New England Journal of Medicine.
Rahul Banerjee, MD, an assistant professor with the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, who wasn’t involved with the research, said the study “is a big deal, and I suspect this will ultimately lead to an FDA [Food and Drug Administration] approval for daratumumab in this setting. If using daratumumab up-front can prevent further myeloma and therefore make patients live longer, this would be immediately adopted at many practices.”
As study first author Meletios Athanasios Dimopoulos, MD, of National and Kapodistrian University of Athens and Alexandra General Hospital in Greece, noted at a news briefing, SMM is common, affecting 0.5% of the population aged over 40, per a 2023 Iceland study.
“Standard practice is close follow-up without immediate intervention. However, this oftentimes ends in organ tissue damage, and hypercalcemia, bone lesions, renal impairment, and anemia,” Dimopoulos said.
According to him, researchers launched the AQUILA study in light of indications that daratumumab may benefit patients with intermediate- and high-risk SMM.
For the study, researchers recruited patients from 2017 to 2019 in 23 countries with confirmed high-risk SMM for ≤ 5 years (median age, 64 [31-86] years; 47%-49% men; 83% White).
In the daratumumab group, the drug was administered in 28-day cycles until cycle 39, 36 months, or disease progression, whichever came first (median treatment duration, 38 months [35 months]).
At 5 years, progression-free survival (PFS) — the primary endpoint — was 63.1% (daratumumab) and 40.8% (active monitoring). Researchers estimated 60-month PFS rates at 63.1% and 40.8%, respectively, and overall response rates were 63.4% vs 2.0% (P < .0001), respectively.
The 60-month overall survival rates were 93.0% and 86.9% (HR, 0.52; 95% CI, 0.27-0.98) with 15 deaths in the daratumumab and 26 in the active monitoring group.
“During the follow-up period, there was continuous improvement in favor of the daratumumab arm,” Dimopoulos said. “Even after treatment was discontinued at 3 years, or even at 5 or 6 years, there was a continuous benefit from treatment with daratumumab.”
By clinical cutoff in May 2024, 65% of patients taking daratumumab had finished 39 cycles/3 years of treatment vs 40.8% in the active monitoring group. Progressive disease was the most common reason that patients stopped treatment (21.8% and 41.8% of patients in the groups, respectively).
Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 40.4% (daratumumab) and 30.1% (active monitoring) of patients. The most common was hypertension (5.7% and 4.6%, respectively).
In the daratumumab group, 5.7% discontinued therapy because of TEAEs, which the researchers described as a “low” number, and fatal TEAEs were similar in both groups (1.0% and 2.0%, respectively).
Banerjee said that “one theoretical risk of using daratumumab monotherapy to treat perceived high-risk SMM is that if the patient actually has active multiple myeloma, you are undertreating them. For anyone with HR-SMM, active multiple myeloma must be completely ruled out. I always insist on both a PET-CT and a whole-body MRI to evaluate the bone marrow comprehensively.”
For now, Banerjee said, clinicians should wait for the US Food and Drug Administration approval before prescribing daratumumab for high-risk SMM.
Are there alternatives to reduce the risk for SMM turning into MM? “Generally, I advise close observation in most cases, but we do have clinical trials in this space,” Banerjee said. “Technically, it is possible to consider lenalidomide monotherapy in SMM based on the results of a large phase 3 study. But lenalidomide is expensive and has many side effects. Insurance companies often won’t cover it fully, and patients almost always have at least one side effect.”
Also, he added, “only half of patients saw their high-risk SMM disease burden drop. Lenalidomide also has a clear link to rare, delayed toxicities such as second primary malignancies, which makes us nervous.”
Janssen Pharmaceuticals, the maker of daratumumab, funded the study. Dimopoulos disclosed ties with Sanofi, Regeneron, Menarini, Takeda, GSK, BMS, Janssen Pharmaceuticals, BeiGene, Swixx, AstraZeneca, and Amgen. Banerjee disclosed ties with AbbVie, Adaptive, BMS, Caribou, Genentech/Roche, GSK, Karyopharm Therapeutics, Legend, Johnson & Johnson, Novartis, Pack, Pfizer, Prothena, Sanofi Pasteur, and SparkCures. Some other authors reported various and multiple disclosures, including ties with Janssen Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Among 390 patients with SMM (194 assigned to daratumumab and 196 to active monitoring), progression to active MM or death over a follow-up of 65.2 (0-76.6) months was 51% lower in the daratumumab group vs active monitoring (34.5% vs 50.5%, hazard ratio [HR], 0.49; 95% CI, 0.36-0.67; P < .0001), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting and in a simultaneous publication in the New England Journal of Medicine.
Rahul Banerjee, MD, an assistant professor with the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, who wasn’t involved with the research, said the study “is a big deal, and I suspect this will ultimately lead to an FDA [Food and Drug Administration] approval for daratumumab in this setting. If using daratumumab up-front can prevent further myeloma and therefore make patients live longer, this would be immediately adopted at many practices.”
As study first author Meletios Athanasios Dimopoulos, MD, of National and Kapodistrian University of Athens and Alexandra General Hospital in Greece, noted at a news briefing, SMM is common, affecting 0.5% of the population aged over 40, per a 2023 Iceland study.
“Standard practice is close follow-up without immediate intervention. However, this oftentimes ends in organ tissue damage, and hypercalcemia, bone lesions, renal impairment, and anemia,” Dimopoulos said.
According to him, researchers launched the AQUILA study in light of indications that daratumumab may benefit patients with intermediate- and high-risk SMM.
For the study, researchers recruited patients from 2017 to 2019 in 23 countries with confirmed high-risk SMM for ≤ 5 years (median age, 64 [31-86] years; 47%-49% men; 83% White).
In the daratumumab group, the drug was administered in 28-day cycles until cycle 39, 36 months, or disease progression, whichever came first (median treatment duration, 38 months [35 months]).
At 5 years, progression-free survival (PFS) — the primary endpoint — was 63.1% (daratumumab) and 40.8% (active monitoring). Researchers estimated 60-month PFS rates at 63.1% and 40.8%, respectively, and overall response rates were 63.4% vs 2.0% (P < .0001), respectively.
The 60-month overall survival rates were 93.0% and 86.9% (HR, 0.52; 95% CI, 0.27-0.98) with 15 deaths in the daratumumab and 26 in the active monitoring group.
“During the follow-up period, there was continuous improvement in favor of the daratumumab arm,” Dimopoulos said. “Even after treatment was discontinued at 3 years, or even at 5 or 6 years, there was a continuous benefit from treatment with daratumumab.”
By clinical cutoff in May 2024, 65% of patients taking daratumumab had finished 39 cycles/3 years of treatment vs 40.8% in the active monitoring group. Progressive disease was the most common reason that patients stopped treatment (21.8% and 41.8% of patients in the groups, respectively).
Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 40.4% (daratumumab) and 30.1% (active monitoring) of patients. The most common was hypertension (5.7% and 4.6%, respectively).
In the daratumumab group, 5.7% discontinued therapy because of TEAEs, which the researchers described as a “low” number, and fatal TEAEs were similar in both groups (1.0% and 2.0%, respectively).
Banerjee said that “one theoretical risk of using daratumumab monotherapy to treat perceived high-risk SMM is that if the patient actually has active multiple myeloma, you are undertreating them. For anyone with HR-SMM, active multiple myeloma must be completely ruled out. I always insist on both a PET-CT and a whole-body MRI to evaluate the bone marrow comprehensively.”
For now, Banerjee said, clinicians should wait for the US Food and Drug Administration approval before prescribing daratumumab for high-risk SMM.
Are there alternatives to reduce the risk for SMM turning into MM? “Generally, I advise close observation in most cases, but we do have clinical trials in this space,” Banerjee said. “Technically, it is possible to consider lenalidomide monotherapy in SMM based on the results of a large phase 3 study. But lenalidomide is expensive and has many side effects. Insurance companies often won’t cover it fully, and patients almost always have at least one side effect.”
Also, he added, “only half of patients saw their high-risk SMM disease burden drop. Lenalidomide also has a clear link to rare, delayed toxicities such as second primary malignancies, which makes us nervous.”
Janssen Pharmaceuticals, the maker of daratumumab, funded the study. Dimopoulos disclosed ties with Sanofi, Regeneron, Menarini, Takeda, GSK, BMS, Janssen Pharmaceuticals, BeiGene, Swixx, AstraZeneca, and Amgen. Banerjee disclosed ties with AbbVie, Adaptive, BMS, Caribou, Genentech/Roche, GSK, Karyopharm Therapeutics, Legend, Johnson & Johnson, Novartis, Pack, Pfizer, Prothena, Sanofi Pasteur, and SparkCures. Some other authors reported various and multiple disclosures, including ties with Janssen Pharmaceuticals.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
Some Antihypertensives Linked to HCC Risk in Patients With MASLD and Cirrhosis
SAN DIEGO — according to new research.
In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.
About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.
However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Analyzing Potential Risks
In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.
Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.
A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.
After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.
However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).
“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.
“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”
Considering Clinical Implications
“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.
The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”
“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.
In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.
Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.
“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”
Elhariri and Butt reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO — according to new research.
In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.
About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.
However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Analyzing Potential Risks
In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.
Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.
A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.
After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.
However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).
“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.
“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”
Considering Clinical Implications
“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.
The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”
“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.
In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.
Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.
“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”
Elhariri and Butt reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO — according to new research.
In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.
About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.
However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Analyzing Potential Risks
In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.
Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.
A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.
After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.
However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).
“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.
“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”
Considering Clinical Implications
“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.
The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”
“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.
In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.
Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.
“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”
Elhariri and Butt reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM AASLD 2024
Wound Healing: Dermatologist’s Toolbox Requires Frequent Updates
NEW YORK CITY — Instructions on wound healing often involve disturbing photographs of severe diabetic ulcers, angry autoimmune blistering, and oozing lesions produced by uncommon genetic disorders, but whether or not they are dramatic, day-to-day dermatologic wound care relies on both the basics as well as novel approaches, according to a well-known wound treatment expert.
, director of the Wound Clinic at Jackson Memorial Hospital and chair of the Department of Dermatology and Cutaneous Surgery at the University of Miami, Florida.
“We as a specialty make and repair more wounds than any other specialty,” said Kirsner, who provided data to make his point. In a table he showed, the number of wound repairs made annually by dermatologists was several-fold higher than surgeons, the next highest group, and the numbers declined rapidly from there.
Speaking at the 27th Annual Winter Symposium – Advances in Medical and Surgical Dermatology (MSWS) 2024, Kirsner offered an array of clinical pearls, reinforced some basics, and pointed to well-supported strategies he believes are too often overlooked.
Drugs Repurposed for Wound Healing
Of the clinical pearls, he spoke of the repurposing of several agents for wound care. His first example was the monoclonal antibody dupilumab, which inhibits interleukin-4 (IL-4) and IL-13 signaling, to heal selected patients with leg ulcers. The potential of this drug for wound healing was based on a patient with a leg ulcer who presented with concomitant prurigo nodularis and biliary cirrhosis. When offered for the comorbidities, dupilumab provided a “dramatic” benefit with regard to the wound, according to Kirsner.
The explanation for the response is that IL-4 and IL-13 have been found to be upregulated in some patients with leg ulcers. Based on numerous cases, Kirsner spoke of a phenotype of nonhealing leg ulcers from which elevated IL-4 and IL-13 can be isolated; these are the candidates for adding dupilumab to wound care, he said.
Topical beta-blockade is another example of a therapy repurposed for wound healing, according to Kirsner. He said beta-blockers are already a standard of care for burn wounds, but the mechanism is relevant in other wound types.
Several studies have looked at this phenomenon, with experimental studies showing that skin healing is impaired when beta-2 receptors are agonized but accelerated when blocked.
Beta-Blockade Accelerates Wound Healing
A recent review of these mechanisms in soft-tissue wound healing pointed to an anti-inflammatory effect, acceleration of keratinocyte migration, pro-reepithelization effects, and inhibition of bacterial virulence. Beta-blockers were first implicated as mediators of wound healing more than a decade ago, but Kirsner indicated that there is now more attention to this therapy within a comprehensive approach in difficult cases.
Although not specific to wound healing, the potential for teprotumumab to improve control of pretibial myxedema is another example of a repurposed therapy for a challenging skin disease. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor-1 (IGF-1) receptor, is approved for active thyroid eye disease, but Kirsner cited data showing compelling evidence of benefit in this cutaneous complication of Graves disease.
As for basics, Kirsner devoted some time to emphasizing the importance of compression therapy for improving leg vascularization. This is not something to just consider; rather, he thinks it is part of standard practice. “Compress all leg ulcers,” was Kirsner’s simple message.
Citing encouraging work in identifying targetable molecular events in wound healing, Kirsner suggested that treatment might be increasingly guided by biomarkers. He pointed to ongoing work to characterize wound exudate as a source of biomarkers.
“The discarded dressing contains a wealth of information,” he said, referring to cell types and proteins, such as growth factors. He thinks that the ongoing studies of exudate, which have shown that molecular processes detected at the periphery are often different than those at the focal site of injury, have substantial promise for identifying new treatment targets.
Virtual Reality to Address Pain
From a practical standpoint, Kirsner looked to a well-studied but still underused adjunct to wound debridement and surgical repair: the distraction offered by relatively low-priced virtual reality systems. He described it as a simple way to help patients keep their minds off the pain. It is not a new idea and has been studied for this use numerous times, and the evidence of benefit is essentially uniform, according to Kirsner.
He said effective and sophisticated systems can now be purchased for just hundreds of dollars, and no training is needed. Indeed, he said pediatric patients can typically explain how the system works if the clinician does not know.
“If you can enhance their experience [during wound repair], you can make their lives and your life better,” he said.
Joshua Zeichner, MD, associate professor of dermatology at Mount Sinai Hospital in New York City, concurred that the evidence supports this approach and is easy to do. “I am in favor of anything that improves the experience of the patient,” said Zeichner, who chaired the portion of the meeting during which Kirsner spoke.
Kirsner said he practices what he preaches. “I routinely employ virtual reality for simple surgical procedures or processes that patients might find unpleasant,” he said. He acknowledged that clinicians might have heard this message before, but he believes those who have not yet introduced this into their practice should consider it.
Kirsner has reported no relevant financial relationships. Zeichner has reported serving as a consultant for Beiersdorf.
A version of this article first appeared on Medscape.com.
NEW YORK CITY — Instructions on wound healing often involve disturbing photographs of severe diabetic ulcers, angry autoimmune blistering, and oozing lesions produced by uncommon genetic disorders, but whether or not they are dramatic, day-to-day dermatologic wound care relies on both the basics as well as novel approaches, according to a well-known wound treatment expert.
, director of the Wound Clinic at Jackson Memorial Hospital and chair of the Department of Dermatology and Cutaneous Surgery at the University of Miami, Florida.
“We as a specialty make and repair more wounds than any other specialty,” said Kirsner, who provided data to make his point. In a table he showed, the number of wound repairs made annually by dermatologists was several-fold higher than surgeons, the next highest group, and the numbers declined rapidly from there.
Speaking at the 27th Annual Winter Symposium – Advances in Medical and Surgical Dermatology (MSWS) 2024, Kirsner offered an array of clinical pearls, reinforced some basics, and pointed to well-supported strategies he believes are too often overlooked.
Drugs Repurposed for Wound Healing
Of the clinical pearls, he spoke of the repurposing of several agents for wound care. His first example was the monoclonal antibody dupilumab, which inhibits interleukin-4 (IL-4) and IL-13 signaling, to heal selected patients with leg ulcers. The potential of this drug for wound healing was based on a patient with a leg ulcer who presented with concomitant prurigo nodularis and biliary cirrhosis. When offered for the comorbidities, dupilumab provided a “dramatic” benefit with regard to the wound, according to Kirsner.
The explanation for the response is that IL-4 and IL-13 have been found to be upregulated in some patients with leg ulcers. Based on numerous cases, Kirsner spoke of a phenotype of nonhealing leg ulcers from which elevated IL-4 and IL-13 can be isolated; these are the candidates for adding dupilumab to wound care, he said.
Topical beta-blockade is another example of a therapy repurposed for wound healing, according to Kirsner. He said beta-blockers are already a standard of care for burn wounds, but the mechanism is relevant in other wound types.
Several studies have looked at this phenomenon, with experimental studies showing that skin healing is impaired when beta-2 receptors are agonized but accelerated when blocked.
Beta-Blockade Accelerates Wound Healing
A recent review of these mechanisms in soft-tissue wound healing pointed to an anti-inflammatory effect, acceleration of keratinocyte migration, pro-reepithelization effects, and inhibition of bacterial virulence. Beta-blockers were first implicated as mediators of wound healing more than a decade ago, but Kirsner indicated that there is now more attention to this therapy within a comprehensive approach in difficult cases.
Although not specific to wound healing, the potential for teprotumumab to improve control of pretibial myxedema is another example of a repurposed therapy for a challenging skin disease. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor-1 (IGF-1) receptor, is approved for active thyroid eye disease, but Kirsner cited data showing compelling evidence of benefit in this cutaneous complication of Graves disease.
As for basics, Kirsner devoted some time to emphasizing the importance of compression therapy for improving leg vascularization. This is not something to just consider; rather, he thinks it is part of standard practice. “Compress all leg ulcers,” was Kirsner’s simple message.
Citing encouraging work in identifying targetable molecular events in wound healing, Kirsner suggested that treatment might be increasingly guided by biomarkers. He pointed to ongoing work to characterize wound exudate as a source of biomarkers.
“The discarded dressing contains a wealth of information,” he said, referring to cell types and proteins, such as growth factors. He thinks that the ongoing studies of exudate, which have shown that molecular processes detected at the periphery are often different than those at the focal site of injury, have substantial promise for identifying new treatment targets.
Virtual Reality to Address Pain
From a practical standpoint, Kirsner looked to a well-studied but still underused adjunct to wound debridement and surgical repair: the distraction offered by relatively low-priced virtual reality systems. He described it as a simple way to help patients keep their minds off the pain. It is not a new idea and has been studied for this use numerous times, and the evidence of benefit is essentially uniform, according to Kirsner.
He said effective and sophisticated systems can now be purchased for just hundreds of dollars, and no training is needed. Indeed, he said pediatric patients can typically explain how the system works if the clinician does not know.
“If you can enhance their experience [during wound repair], you can make their lives and your life better,” he said.
Joshua Zeichner, MD, associate professor of dermatology at Mount Sinai Hospital in New York City, concurred that the evidence supports this approach and is easy to do. “I am in favor of anything that improves the experience of the patient,” said Zeichner, who chaired the portion of the meeting during which Kirsner spoke.
Kirsner said he practices what he preaches. “I routinely employ virtual reality for simple surgical procedures or processes that patients might find unpleasant,” he said. He acknowledged that clinicians might have heard this message before, but he believes those who have not yet introduced this into their practice should consider it.
Kirsner has reported no relevant financial relationships. Zeichner has reported serving as a consultant for Beiersdorf.
A version of this article first appeared on Medscape.com.
NEW YORK CITY — Instructions on wound healing often involve disturbing photographs of severe diabetic ulcers, angry autoimmune blistering, and oozing lesions produced by uncommon genetic disorders, but whether or not they are dramatic, day-to-day dermatologic wound care relies on both the basics as well as novel approaches, according to a well-known wound treatment expert.
, director of the Wound Clinic at Jackson Memorial Hospital and chair of the Department of Dermatology and Cutaneous Surgery at the University of Miami, Florida.
“We as a specialty make and repair more wounds than any other specialty,” said Kirsner, who provided data to make his point. In a table he showed, the number of wound repairs made annually by dermatologists was several-fold higher than surgeons, the next highest group, and the numbers declined rapidly from there.
Speaking at the 27th Annual Winter Symposium – Advances in Medical and Surgical Dermatology (MSWS) 2024, Kirsner offered an array of clinical pearls, reinforced some basics, and pointed to well-supported strategies he believes are too often overlooked.
Drugs Repurposed for Wound Healing
Of the clinical pearls, he spoke of the repurposing of several agents for wound care. His first example was the monoclonal antibody dupilumab, which inhibits interleukin-4 (IL-4) and IL-13 signaling, to heal selected patients with leg ulcers. The potential of this drug for wound healing was based on a patient with a leg ulcer who presented with concomitant prurigo nodularis and biliary cirrhosis. When offered for the comorbidities, dupilumab provided a “dramatic” benefit with regard to the wound, according to Kirsner.
The explanation for the response is that IL-4 and IL-13 have been found to be upregulated in some patients with leg ulcers. Based on numerous cases, Kirsner spoke of a phenotype of nonhealing leg ulcers from which elevated IL-4 and IL-13 can be isolated; these are the candidates for adding dupilumab to wound care, he said.
Topical beta-blockade is another example of a therapy repurposed for wound healing, according to Kirsner. He said beta-blockers are already a standard of care for burn wounds, but the mechanism is relevant in other wound types.
Several studies have looked at this phenomenon, with experimental studies showing that skin healing is impaired when beta-2 receptors are agonized but accelerated when blocked.
Beta-Blockade Accelerates Wound Healing
A recent review of these mechanisms in soft-tissue wound healing pointed to an anti-inflammatory effect, acceleration of keratinocyte migration, pro-reepithelization effects, and inhibition of bacterial virulence. Beta-blockers were first implicated as mediators of wound healing more than a decade ago, but Kirsner indicated that there is now more attention to this therapy within a comprehensive approach in difficult cases.
Although not specific to wound healing, the potential for teprotumumab to improve control of pretibial myxedema is another example of a repurposed therapy for a challenging skin disease. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor-1 (IGF-1) receptor, is approved for active thyroid eye disease, but Kirsner cited data showing compelling evidence of benefit in this cutaneous complication of Graves disease.
As for basics, Kirsner devoted some time to emphasizing the importance of compression therapy for improving leg vascularization. This is not something to just consider; rather, he thinks it is part of standard practice. “Compress all leg ulcers,” was Kirsner’s simple message.
Citing encouraging work in identifying targetable molecular events in wound healing, Kirsner suggested that treatment might be increasingly guided by biomarkers. He pointed to ongoing work to characterize wound exudate as a source of biomarkers.
“The discarded dressing contains a wealth of information,” he said, referring to cell types and proteins, such as growth factors. He thinks that the ongoing studies of exudate, which have shown that molecular processes detected at the periphery are often different than those at the focal site of injury, have substantial promise for identifying new treatment targets.
Virtual Reality to Address Pain
From a practical standpoint, Kirsner looked to a well-studied but still underused adjunct to wound debridement and surgical repair: the distraction offered by relatively low-priced virtual reality systems. He described it as a simple way to help patients keep their minds off the pain. It is not a new idea and has been studied for this use numerous times, and the evidence of benefit is essentially uniform, according to Kirsner.
He said effective and sophisticated systems can now be purchased for just hundreds of dollars, and no training is needed. Indeed, he said pediatric patients can typically explain how the system works if the clinician does not know.
“If you can enhance their experience [during wound repair], you can make their lives and your life better,” he said.
Joshua Zeichner, MD, associate professor of dermatology at Mount Sinai Hospital in New York City, concurred that the evidence supports this approach and is easy to do. “I am in favor of anything that improves the experience of the patient,” said Zeichner, who chaired the portion of the meeting during which Kirsner spoke.
Kirsner said he practices what he preaches. “I routinely employ virtual reality for simple surgical procedures or processes that patients might find unpleasant,” he said. He acknowledged that clinicians might have heard this message before, but he believes those who have not yet introduced this into their practice should consider it.
Kirsner has reported no relevant financial relationships. Zeichner has reported serving as a consultant for Beiersdorf.
A version of this article first appeared on Medscape.com.
FROM MSWS 2024
Tapering Corticosteroids in Severe Alcohol-Associated Hepatitis Appears Safe
SAN DIEGO — , according to new research.
“Although several drugs have been evaluated for severe alcohol-associated hepatitis, none have succeeded in practice. Corticosteroids remain the mainstay of treatment; however, infections remain a major concern in 25%-40% of cases,” said Anand Kulkarni, MD, senior consultant and director of critical care hepatology at the Asian Institute of Gastroenterology in Hyderabad, India.
“There are no standard society guidelines for steroid dosing, and our current practices stem from studies in the 1970s, so there’s a major knowledge gap around optimal dosing and if stepwise tapering helps,” said Kulkarni, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Assessing Tapered Doses
In a multicenter, open-label randomized controlled trial, 254 patients with SAH from four Indian centers and one Canadian center were randomized to receive either a fixed or tapering dose of 40 mg prednisolone daily for 4 weeks. The patients in the tapering group received a starting dose of 40 mg, which was reduced by 10 mg weekly over 4 weeks.
While taking corticosteroids, 66% of those in the fixed dose group and 55% of those in the tapering group also received prophylactic antibiotics.
The mean age of participants was 41.1 years, the median Model For End-Stage Liver Disease score was 25.6, and 98.4% were men.
The primary objective was to compare the incidence of drug-related adverse events, infections, hospitalization, and mortality through day 90.
The duration of corticosteroid therapy was 22 days in the fixed dose group and 23 days in the tapering dose group.
Overall, the proportion of steroid responders was similar in both groups, at 80.3% in the fixed dose group and 82.5% in the tapering dose group.
However, the incidence of drug-related adverse events was significantly higher in the fixed dose group (52%) than in the tapering dose group (36.2%). The most common adverse events in both groups were infection, hyperglycemia, and hematochezia.
At 90 days, the incidence of infection was significantly lower in the tapering group (19.7%) than in the fixed dose group (33.1%). In both groups, the most common infection sites were the lungs (28.3%) and urinary tract (22.4%).
In terms of liver-related outcomes, some patients developed hepatic encephalopathy (11.8% in fixed dose vs 6.3% in tapering dose) and acute variceal bleed (3.1% in each group), as well as acute kidney injury (26.8% in fixed dose vs 18.9% in tapering dose).
Hospitalization within 90 days was required in 44.1% of the fixed dose group and 33.1% of the tapering dose group.
Survival at day 90 was 83.5% in the fixed dose group and 86.6% in the tapering dose group. Four patients in the fixed dose group and three patients in the tapering dose group underwent living donor liver transplantation by day 90.
Relapse of alcohol use by day 90 occurred in 13.4% of the fixed dose group and 12.6% of the tapering dose group.
“Rapid tapering in severe alcohol-associated hepatitis reduces infections and hospitalizations but doesn’t have a significant impact on survival,” Kulkarni concluded.
Considering Alternative Therapies
Given the high risk for infection in patients with SAH and limited certainty around benefits, the data may also call into question whether to give steroids to these patients at all, said session co-moderator Aleksander Krag, MD, professor of clinical medicine at the University of Southern Denmark, Odense, Denmark, and secretary general of the European Association for the Study of Liver 2023-2025.
“Since there are no other treatments available as of now, we’ll still continue to give steroids,” Kulkarni noted. But “tapering the dose should be beneficial.”
Although steroid therapy has been considered the “mainstay treatment” for SAH for 50 years, it doesn’t always lead to long-term improvement in liver values or survival, said Prasun Jalal, MD, the Stan and Sue Partee Endowed Chair in Hepatology at Baylor College of Medicine, Houston, who wasn’t involved with the study.
Researchers are looking to other connections, such as the gut microbiome, to find treatments for advanced alcoholic liver disease, Jalal said in an interview. In a small pilot study, he and colleagues found that intestinal microbiota transplantation (IMT) appears to be safe and effective for these patients.
“Early analyses suggest that IMT has a favorable outcome on the prognosis of patients with severe alcohol-associated hepatitis and is safe,” Jalal said. “A longer follow-up study with a larger sample size is in progress.”
Kulkarni and Krag reported no relevant disclosures. Jalal has speaking and teaching relationships with AbbVie and Madrigal.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
“Although several drugs have been evaluated for severe alcohol-associated hepatitis, none have succeeded in practice. Corticosteroids remain the mainstay of treatment; however, infections remain a major concern in 25%-40% of cases,” said Anand Kulkarni, MD, senior consultant and director of critical care hepatology at the Asian Institute of Gastroenterology in Hyderabad, India.
“There are no standard society guidelines for steroid dosing, and our current practices stem from studies in the 1970s, so there’s a major knowledge gap around optimal dosing and if stepwise tapering helps,” said Kulkarni, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Assessing Tapered Doses
In a multicenter, open-label randomized controlled trial, 254 patients with SAH from four Indian centers and one Canadian center were randomized to receive either a fixed or tapering dose of 40 mg prednisolone daily for 4 weeks. The patients in the tapering group received a starting dose of 40 mg, which was reduced by 10 mg weekly over 4 weeks.
While taking corticosteroids, 66% of those in the fixed dose group and 55% of those in the tapering group also received prophylactic antibiotics.
The mean age of participants was 41.1 years, the median Model For End-Stage Liver Disease score was 25.6, and 98.4% were men.
The primary objective was to compare the incidence of drug-related adverse events, infections, hospitalization, and mortality through day 90.
The duration of corticosteroid therapy was 22 days in the fixed dose group and 23 days in the tapering dose group.
Overall, the proportion of steroid responders was similar in both groups, at 80.3% in the fixed dose group and 82.5% in the tapering dose group.
However, the incidence of drug-related adverse events was significantly higher in the fixed dose group (52%) than in the tapering dose group (36.2%). The most common adverse events in both groups were infection, hyperglycemia, and hematochezia.
At 90 days, the incidence of infection was significantly lower in the tapering group (19.7%) than in the fixed dose group (33.1%). In both groups, the most common infection sites were the lungs (28.3%) and urinary tract (22.4%).
In terms of liver-related outcomes, some patients developed hepatic encephalopathy (11.8% in fixed dose vs 6.3% in tapering dose) and acute variceal bleed (3.1% in each group), as well as acute kidney injury (26.8% in fixed dose vs 18.9% in tapering dose).
Hospitalization within 90 days was required in 44.1% of the fixed dose group and 33.1% of the tapering dose group.
Survival at day 90 was 83.5% in the fixed dose group and 86.6% in the tapering dose group. Four patients in the fixed dose group and three patients in the tapering dose group underwent living donor liver transplantation by day 90.
Relapse of alcohol use by day 90 occurred in 13.4% of the fixed dose group and 12.6% of the tapering dose group.
“Rapid tapering in severe alcohol-associated hepatitis reduces infections and hospitalizations but doesn’t have a significant impact on survival,” Kulkarni concluded.
Considering Alternative Therapies
Given the high risk for infection in patients with SAH and limited certainty around benefits, the data may also call into question whether to give steroids to these patients at all, said session co-moderator Aleksander Krag, MD, professor of clinical medicine at the University of Southern Denmark, Odense, Denmark, and secretary general of the European Association for the Study of Liver 2023-2025.
“Since there are no other treatments available as of now, we’ll still continue to give steroids,” Kulkarni noted. But “tapering the dose should be beneficial.”
Although steroid therapy has been considered the “mainstay treatment” for SAH for 50 years, it doesn’t always lead to long-term improvement in liver values or survival, said Prasun Jalal, MD, the Stan and Sue Partee Endowed Chair in Hepatology at Baylor College of Medicine, Houston, who wasn’t involved with the study.
Researchers are looking to other connections, such as the gut microbiome, to find treatments for advanced alcoholic liver disease, Jalal said in an interview. In a small pilot study, he and colleagues found that intestinal microbiota transplantation (IMT) appears to be safe and effective for these patients.
“Early analyses suggest that IMT has a favorable outcome on the prognosis of patients with severe alcohol-associated hepatitis and is safe,” Jalal said. “A longer follow-up study with a larger sample size is in progress.”
Kulkarni and Krag reported no relevant disclosures. Jalal has speaking and teaching relationships with AbbVie and Madrigal.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
“Although several drugs have been evaluated for severe alcohol-associated hepatitis, none have succeeded in practice. Corticosteroids remain the mainstay of treatment; however, infections remain a major concern in 25%-40% of cases,” said Anand Kulkarni, MD, senior consultant and director of critical care hepatology at the Asian Institute of Gastroenterology in Hyderabad, India.
“There are no standard society guidelines for steroid dosing, and our current practices stem from studies in the 1970s, so there’s a major knowledge gap around optimal dosing and if stepwise tapering helps,” said Kulkarni, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Assessing Tapered Doses
In a multicenter, open-label randomized controlled trial, 254 patients with SAH from four Indian centers and one Canadian center were randomized to receive either a fixed or tapering dose of 40 mg prednisolone daily for 4 weeks. The patients in the tapering group received a starting dose of 40 mg, which was reduced by 10 mg weekly over 4 weeks.
While taking corticosteroids, 66% of those in the fixed dose group and 55% of those in the tapering group also received prophylactic antibiotics.
The mean age of participants was 41.1 years, the median Model For End-Stage Liver Disease score was 25.6, and 98.4% were men.
The primary objective was to compare the incidence of drug-related adverse events, infections, hospitalization, and mortality through day 90.
The duration of corticosteroid therapy was 22 days in the fixed dose group and 23 days in the tapering dose group.
Overall, the proportion of steroid responders was similar in both groups, at 80.3% in the fixed dose group and 82.5% in the tapering dose group.
However, the incidence of drug-related adverse events was significantly higher in the fixed dose group (52%) than in the tapering dose group (36.2%). The most common adverse events in both groups were infection, hyperglycemia, and hematochezia.
At 90 days, the incidence of infection was significantly lower in the tapering group (19.7%) than in the fixed dose group (33.1%). In both groups, the most common infection sites were the lungs (28.3%) and urinary tract (22.4%).
In terms of liver-related outcomes, some patients developed hepatic encephalopathy (11.8% in fixed dose vs 6.3% in tapering dose) and acute variceal bleed (3.1% in each group), as well as acute kidney injury (26.8% in fixed dose vs 18.9% in tapering dose).
Hospitalization within 90 days was required in 44.1% of the fixed dose group and 33.1% of the tapering dose group.
Survival at day 90 was 83.5% in the fixed dose group and 86.6% in the tapering dose group. Four patients in the fixed dose group and three patients in the tapering dose group underwent living donor liver transplantation by day 90.
Relapse of alcohol use by day 90 occurred in 13.4% of the fixed dose group and 12.6% of the tapering dose group.
“Rapid tapering in severe alcohol-associated hepatitis reduces infections and hospitalizations but doesn’t have a significant impact on survival,” Kulkarni concluded.
Considering Alternative Therapies
Given the high risk for infection in patients with SAH and limited certainty around benefits, the data may also call into question whether to give steroids to these patients at all, said session co-moderator Aleksander Krag, MD, professor of clinical medicine at the University of Southern Denmark, Odense, Denmark, and secretary general of the European Association for the Study of Liver 2023-2025.
“Since there are no other treatments available as of now, we’ll still continue to give steroids,” Kulkarni noted. But “tapering the dose should be beneficial.”
Although steroid therapy has been considered the “mainstay treatment” for SAH for 50 years, it doesn’t always lead to long-term improvement in liver values or survival, said Prasun Jalal, MD, the Stan and Sue Partee Endowed Chair in Hepatology at Baylor College of Medicine, Houston, who wasn’t involved with the study.
Researchers are looking to other connections, such as the gut microbiome, to find treatments for advanced alcoholic liver disease, Jalal said in an interview. In a small pilot study, he and colleagues found that intestinal microbiota transplantation (IMT) appears to be safe and effective for these patients.
“Early analyses suggest that IMT has a favorable outcome on the prognosis of patients with severe alcohol-associated hepatitis and is safe,” Jalal said. “A longer follow-up study with a larger sample size is in progress.”
Kulkarni and Krag reported no relevant disclosures. Jalal has speaking and teaching relationships with AbbVie and Madrigal.
A version of this article appeared on Medscape.com.
FROM AASLD 2024
Multiple Myeloma: Dexamethasone-Sparing Approach Benefits Frail Older Adults
The study “is the first randomized phase 3 study dedicated to frail patients,” said first author Salomon Manier, MD, PhD, an associate professor of hematology at Lille University Hospital, Lille, France. He presented the findings this week at the American Society of Hematology (ASH) 2024 Annual Meeting in San Diego.
“It shows that daratumumab-lenalidomide [with limited dexamethasone] led to a significant reduced risk of progression or death by 49% in frail patients, with a favorable safety profile and an improved health-related quality of life,” Manier said.
Older adult patients who are newly diagnosed with MM have varying levels of fitness or frailty and have been shown to have shorter survival, with higher rates of nonhematologic adverse events and treatment discontinuation.
While the regimen of daratumumab, lenalidomide, and dexamethasone has become a standard of care, with efficacy and tolerance, including for patients with frailty, the infection and pneumonia rates with the approach can be high, particularly for patients with frailty.
To evaluate if an alternative, dexamethasone-sparing approach could improve outcomes while limiting toxicity for older adults, Manier and his colleagues conducted the prospective, open-label phase 3 IFM2017-03 trial, involving 295 patients (age, 65 years) with newly diagnosed MM at 90 centers in France.
The patients had a median age of 81, with 84% older than 75 years and 61% older than 80 years. All had an Eastern Cooperative Oncology Group proxy frailty score ≥ 2.
The patients were randomized 1:2 to treatment either with the Rd regimen of 28-day cycles of lenalidomide (25 mg/d, 21/28) and dexamethasone (20 mg once weekly) or with the dexamethasone-sparing regimen (DR) of daratumumab (1800 mg subcutaneous once weekly for 8 weeks, once every 2 weeks for 16 weeks, and once every 4 weeks thereafter), lenalidomide (25 mg/d, 21/28), and two cycles of dexamethasone (20 mg once weekly for 8 weeks then stopping).
The randomization included stratification based on age and cancer stage. Baseline characteristics were well balanced in the two groups.
Both regimens were administered until disease progression or unacceptable toxicity.
As of the data cut-off in November 2024, with a median follow-up of 46.3 months, 81 of the original 200 patients in the DR arm remained on treatment, and 11 of 95 continued in the Rd arm.
The overall median treatment duration among the 200 original patients in the DR arm was 31.6 months and 14.3 months in the Rd arm.
The study met its primary endpoint of progression-free survival (PFS), with a median rate of 53.4 months in the DR arm vs 22.5 months in the Rd arm (hazard ratio [HR], 0.51; P < .0001).
The improved PFS in the DR arm was observed across all subgroups based on age, Charlson comorbidity index, cancer stage, cytogenetics, and creatinine clearance; however, those with lower frailty scores had better outcomes in both groups.
A median overall survival was not reached in the DR arm vs 47.2 months in the Rd arm (HR, 0.52; P = .0001).
The DR arm also showed a higher overall best response rate of 94% vs 86% (P = .005), respectively, with deeper responses in the DR arm at all time points, including the earliest points at 4 months.
In terms of adverse events (AEs), at least one AE of grade ≥ 3 occurred in 89% in the DR arm and 79% in the Rd arm.
Those in the DR arm had significantly more grade 3 or higher hematologic AEs with neutropenia (62% vs 34%); however, grade ≥ 3 infections were similar, with 19% in the DR arm and 21% in the Rd arm. Infections involving pneumonia occurred in 6% and 8%, respectively.
There were no significant differences between the two arms in discontinuations due to AEs (30% in the DR arm and 34% in the Rd arm).
While health-related quality of life measures at baseline were well balanced between the two groups, those in the DR arm reported significantly shorter times to clinically meaningful improvement in all domains of the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30).
“The safety profile was significantly improved and was favorable, without increased infection or pneumonia rates, with similar rates of treatment discontinuation,” Manier said.
Based on the findings, “we believe that the dexamethasone-sparing strategy is effective and safe for treating these frail patients with multiple myeloma,” he added.
Commenting on the study, Manni Mohyuddin, MD, an assistant professor in the multiple myeloma program at the Huntsman Cancer Institute, University of Utah, Salt Lake City, noted that, with the popularity of triplet regimens such as daratumumab, lenalidomide, and dexamethasone, the Rd regimen in the study is not as commonly used.
“But what this trial tells us is that efficacy outcomes in such a group of patients are encouraging despite getting rid of dexamethasone so quickly,” he said in an interview.
However, “while the tide is changing, dexamethasone is still given long-term, week after week after week in most myeloma protocols and in the community,” he noted. “Hopefully, this trial, and some of the other work, will lead to a change in this space.”
Mohyuddin suggests one approach can involve starting off with just daratumumab and a low dose of dexamethasone, then adding lenalidomide at a lower dose later in a sequential/graded approach.
“Other approaches that should be studied should be bispecific antibodies used sparingly, with less frequent dosing, or finite period,” he added. “There is lot to refine.”
Mohyuddin added a critique that the study’s endpoint of PFS may not have been ideal for the population of elderly and frail patients.
“Older people generally prioritize functional independence and quality of life, and perhaps a more patient-centered endpoint could have led to an even more informative study,” he said.
Manier’s disclosures included consultancy with Takeda Pharmaceuticals, Sanofi, Novartis, Janssen, GlaxoSmithKline, Celgene/BMS, Amgen, Adaptive Biotechnologies, Roche, Regeneron, and AbbVie. Mohyuddin had no disclosures.
A version of this article appeared on Medscape.com.
The study “is the first randomized phase 3 study dedicated to frail patients,” said first author Salomon Manier, MD, PhD, an associate professor of hematology at Lille University Hospital, Lille, France. He presented the findings this week at the American Society of Hematology (ASH) 2024 Annual Meeting in San Diego.
“It shows that daratumumab-lenalidomide [with limited dexamethasone] led to a significant reduced risk of progression or death by 49% in frail patients, with a favorable safety profile and an improved health-related quality of life,” Manier said.
Older adult patients who are newly diagnosed with MM have varying levels of fitness or frailty and have been shown to have shorter survival, with higher rates of nonhematologic adverse events and treatment discontinuation.
While the regimen of daratumumab, lenalidomide, and dexamethasone has become a standard of care, with efficacy and tolerance, including for patients with frailty, the infection and pneumonia rates with the approach can be high, particularly for patients with frailty.
To evaluate if an alternative, dexamethasone-sparing approach could improve outcomes while limiting toxicity for older adults, Manier and his colleagues conducted the prospective, open-label phase 3 IFM2017-03 trial, involving 295 patients (age, 65 years) with newly diagnosed MM at 90 centers in France.
The patients had a median age of 81, with 84% older than 75 years and 61% older than 80 years. All had an Eastern Cooperative Oncology Group proxy frailty score ≥ 2.
The patients were randomized 1:2 to treatment either with the Rd regimen of 28-day cycles of lenalidomide (25 mg/d, 21/28) and dexamethasone (20 mg once weekly) or with the dexamethasone-sparing regimen (DR) of daratumumab (1800 mg subcutaneous once weekly for 8 weeks, once every 2 weeks for 16 weeks, and once every 4 weeks thereafter), lenalidomide (25 mg/d, 21/28), and two cycles of dexamethasone (20 mg once weekly for 8 weeks then stopping).
The randomization included stratification based on age and cancer stage. Baseline characteristics were well balanced in the two groups.
Both regimens were administered until disease progression or unacceptable toxicity.
As of the data cut-off in November 2024, with a median follow-up of 46.3 months, 81 of the original 200 patients in the DR arm remained on treatment, and 11 of 95 continued in the Rd arm.
The overall median treatment duration among the 200 original patients in the DR arm was 31.6 months and 14.3 months in the Rd arm.
The study met its primary endpoint of progression-free survival (PFS), with a median rate of 53.4 months in the DR arm vs 22.5 months in the Rd arm (hazard ratio [HR], 0.51; P < .0001).
The improved PFS in the DR arm was observed across all subgroups based on age, Charlson comorbidity index, cancer stage, cytogenetics, and creatinine clearance; however, those with lower frailty scores had better outcomes in both groups.
A median overall survival was not reached in the DR arm vs 47.2 months in the Rd arm (HR, 0.52; P = .0001).
The DR arm also showed a higher overall best response rate of 94% vs 86% (P = .005), respectively, with deeper responses in the DR arm at all time points, including the earliest points at 4 months.
In terms of adverse events (AEs), at least one AE of grade ≥ 3 occurred in 89% in the DR arm and 79% in the Rd arm.
Those in the DR arm had significantly more grade 3 or higher hematologic AEs with neutropenia (62% vs 34%); however, grade ≥ 3 infections were similar, with 19% in the DR arm and 21% in the Rd arm. Infections involving pneumonia occurred in 6% and 8%, respectively.
There were no significant differences between the two arms in discontinuations due to AEs (30% in the DR arm and 34% in the Rd arm).
While health-related quality of life measures at baseline were well balanced between the two groups, those in the DR arm reported significantly shorter times to clinically meaningful improvement in all domains of the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30).
“The safety profile was significantly improved and was favorable, without increased infection or pneumonia rates, with similar rates of treatment discontinuation,” Manier said.
Based on the findings, “we believe that the dexamethasone-sparing strategy is effective and safe for treating these frail patients with multiple myeloma,” he added.
Commenting on the study, Manni Mohyuddin, MD, an assistant professor in the multiple myeloma program at the Huntsman Cancer Institute, University of Utah, Salt Lake City, noted that, with the popularity of triplet regimens such as daratumumab, lenalidomide, and dexamethasone, the Rd regimen in the study is not as commonly used.
“But what this trial tells us is that efficacy outcomes in such a group of patients are encouraging despite getting rid of dexamethasone so quickly,” he said in an interview.
However, “while the tide is changing, dexamethasone is still given long-term, week after week after week in most myeloma protocols and in the community,” he noted. “Hopefully, this trial, and some of the other work, will lead to a change in this space.”
Mohyuddin suggests one approach can involve starting off with just daratumumab and a low dose of dexamethasone, then adding lenalidomide at a lower dose later in a sequential/graded approach.
“Other approaches that should be studied should be bispecific antibodies used sparingly, with less frequent dosing, or finite period,” he added. “There is lot to refine.”
Mohyuddin added a critique that the study’s endpoint of PFS may not have been ideal for the population of elderly and frail patients.
“Older people generally prioritize functional independence and quality of life, and perhaps a more patient-centered endpoint could have led to an even more informative study,” he said.
Manier’s disclosures included consultancy with Takeda Pharmaceuticals, Sanofi, Novartis, Janssen, GlaxoSmithKline, Celgene/BMS, Amgen, Adaptive Biotechnologies, Roche, Regeneron, and AbbVie. Mohyuddin had no disclosures.
A version of this article appeared on Medscape.com.
The study “is the first randomized phase 3 study dedicated to frail patients,” said first author Salomon Manier, MD, PhD, an associate professor of hematology at Lille University Hospital, Lille, France. He presented the findings this week at the American Society of Hematology (ASH) 2024 Annual Meeting in San Diego.
“It shows that daratumumab-lenalidomide [with limited dexamethasone] led to a significant reduced risk of progression or death by 49% in frail patients, with a favorable safety profile and an improved health-related quality of life,” Manier said.
Older adult patients who are newly diagnosed with MM have varying levels of fitness or frailty and have been shown to have shorter survival, with higher rates of nonhematologic adverse events and treatment discontinuation.
While the regimen of daratumumab, lenalidomide, and dexamethasone has become a standard of care, with efficacy and tolerance, including for patients with frailty, the infection and pneumonia rates with the approach can be high, particularly for patients with frailty.
To evaluate if an alternative, dexamethasone-sparing approach could improve outcomes while limiting toxicity for older adults, Manier and his colleagues conducted the prospective, open-label phase 3 IFM2017-03 trial, involving 295 patients (age, 65 years) with newly diagnosed MM at 90 centers in France.
The patients had a median age of 81, with 84% older than 75 years and 61% older than 80 years. All had an Eastern Cooperative Oncology Group proxy frailty score ≥ 2.
The patients were randomized 1:2 to treatment either with the Rd regimen of 28-day cycles of lenalidomide (25 mg/d, 21/28) and dexamethasone (20 mg once weekly) or with the dexamethasone-sparing regimen (DR) of daratumumab (1800 mg subcutaneous once weekly for 8 weeks, once every 2 weeks for 16 weeks, and once every 4 weeks thereafter), lenalidomide (25 mg/d, 21/28), and two cycles of dexamethasone (20 mg once weekly for 8 weeks then stopping).
The randomization included stratification based on age and cancer stage. Baseline characteristics were well balanced in the two groups.
Both regimens were administered until disease progression or unacceptable toxicity.
As of the data cut-off in November 2024, with a median follow-up of 46.3 months, 81 of the original 200 patients in the DR arm remained on treatment, and 11 of 95 continued in the Rd arm.
The overall median treatment duration among the 200 original patients in the DR arm was 31.6 months and 14.3 months in the Rd arm.
The study met its primary endpoint of progression-free survival (PFS), with a median rate of 53.4 months in the DR arm vs 22.5 months in the Rd arm (hazard ratio [HR], 0.51; P < .0001).
The improved PFS in the DR arm was observed across all subgroups based on age, Charlson comorbidity index, cancer stage, cytogenetics, and creatinine clearance; however, those with lower frailty scores had better outcomes in both groups.
A median overall survival was not reached in the DR arm vs 47.2 months in the Rd arm (HR, 0.52; P = .0001).
The DR arm also showed a higher overall best response rate of 94% vs 86% (P = .005), respectively, with deeper responses in the DR arm at all time points, including the earliest points at 4 months.
In terms of adverse events (AEs), at least one AE of grade ≥ 3 occurred in 89% in the DR arm and 79% in the Rd arm.
Those in the DR arm had significantly more grade 3 or higher hematologic AEs with neutropenia (62% vs 34%); however, grade ≥ 3 infections were similar, with 19% in the DR arm and 21% in the Rd arm. Infections involving pneumonia occurred in 6% and 8%, respectively.
There were no significant differences between the two arms in discontinuations due to AEs (30% in the DR arm and 34% in the Rd arm).
While health-related quality of life measures at baseline were well balanced between the two groups, those in the DR arm reported significantly shorter times to clinically meaningful improvement in all domains of the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30).
“The safety profile was significantly improved and was favorable, without increased infection or pneumonia rates, with similar rates of treatment discontinuation,” Manier said.
Based on the findings, “we believe that the dexamethasone-sparing strategy is effective and safe for treating these frail patients with multiple myeloma,” he added.
Commenting on the study, Manni Mohyuddin, MD, an assistant professor in the multiple myeloma program at the Huntsman Cancer Institute, University of Utah, Salt Lake City, noted that, with the popularity of triplet regimens such as daratumumab, lenalidomide, and dexamethasone, the Rd regimen in the study is not as commonly used.
“But what this trial tells us is that efficacy outcomes in such a group of patients are encouraging despite getting rid of dexamethasone so quickly,” he said in an interview.
However, “while the tide is changing, dexamethasone is still given long-term, week after week after week in most myeloma protocols and in the community,” he noted. “Hopefully, this trial, and some of the other work, will lead to a change in this space.”
Mohyuddin suggests one approach can involve starting off with just daratumumab and a low dose of dexamethasone, then adding lenalidomide at a lower dose later in a sequential/graded approach.
“Other approaches that should be studied should be bispecific antibodies used sparingly, with less frequent dosing, or finite period,” he added. “There is lot to refine.”
Mohyuddin added a critique that the study’s endpoint of PFS may not have been ideal for the population of elderly and frail patients.
“Older people generally prioritize functional independence and quality of life, and perhaps a more patient-centered endpoint could have led to an even more informative study,” he said.
Manier’s disclosures included consultancy with Takeda Pharmaceuticals, Sanofi, Novartis, Janssen, GlaxoSmithKline, Celgene/BMS, Amgen, Adaptive Biotechnologies, Roche, Regeneron, and AbbVie. Mohyuddin had no disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
Women Largely Unaware of Anti-Seizure Med Risks, More Education Needed
LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.
In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.
“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.
She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.
The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
Unique Survey
Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.
The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.
The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.
Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.
The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.
When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.
The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.
ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.
There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.
For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.
ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.
However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.
Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.
They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.
“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.
No Trickle-Down Effect
Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.
“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.
“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.
Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”
She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.
But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”
The investigators and Pack reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.
In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.
“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.
She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.
The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
Unique Survey
Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.
The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.
The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.
Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.
The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.
When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.
The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.
ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.
There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.
For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.
ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.
However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.
Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.
They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.
“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.
No Trickle-Down Effect
Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.
“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.
“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.
Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”
She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.
But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”
The investigators and Pack reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.
In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.
“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.
She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.
The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
Unique Survey
Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.
The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.
The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.
Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.
The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.
When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.
The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.
ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.
There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.
For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.
ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.
However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.
Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.
They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.
“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.
No Trickle-Down Effect
Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.
“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.
“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.
Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”
She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.
But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”
The investigators and Pack reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM AES 2024
Few Focal Epilepsy Cases Controlled by Initial ASM Treatment
LOS ANGELES — Only about 27% of patients newly diagnosed with focal epilepsy are seizure-free on initial anti-seizure medications (ASMs), new research suggested.
This is sobering information to pass on to patients with focal epilepsy who may have high expectations based on prior data. “Patients tend to expect things to happen quickly, said study investigator Sarah Barnard, MD, a research fellow at the School of Translational Medicine, Monash University, Melbourne, Australia.
The study was presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
An International Collaboration
The study is part of the International Human Epilepsy Project (HEP), which focuses on new-onset focal epilepsy, one of the most common forms of the disorder. The researchers are aiming to identify factors that influence treatment response in this population.
For example, they will investigate how specific medications and coexisting conditions affect treatment outcomes. Ultimately, the goal is to enable the development of individualized treatment plans for patients, leading to faster and more effective improvements or potential cures for the condition.
“The investigators wanted to focus in on focal epilepsy and exclude patients with more severe phenotypes, such as those with developmental delays or significant brain injury,” said Barnard. Individuals with focal epilepsy are generally healthy, she added.
In addition, previous studies may have used differing definitions of seizure freedom, said Barnard.
The study included 448 patients, median age about 33 years and 60% women, with focal epilepsy who were enrolled at 34 tertiary epilepsy centers in the United States, Europe, and Australia within 4 months of initiating ASM treatment.
Participants were followed for up to 6 years (the median was 3.13 years). The median age at seizure onset was 29 years, and the median age of treatment initiation was 32 years. The most common first-line ASMs were levetiracetam (56.9%) and lamotrigine (16.5%).
Researchers used updated International League Against Epilepsy definitions. Seizure freedom is defined as no seizures for 12 months or three times the longest pretreatment seizure-free interval, whichever is longer.
Results showed that only 27% of patients were seizure-free in the first year after diagnosis even accounting for a 2-month “medication adjustment” period.
Managing Expectations
Although the study excluded individuals with more severe types of epilepsy, “we still identified a substantial proportion of treatment-resistant cases, suggesting that much more complex factors are at play,” said Jacqueline French, MD, a study coinvestigator and professor at the NYU Langone’s Comprehensive Epilepsy Center in New York City.
“I don’t think we adequately prepare our patients for the challenges of the first year, which can be quite turbulent,” French said.
However, the seizure freedom rate in this study is lower than previous estimates. “It’s much less than what was predicted in other studies, some of which quote around 50%-55% seizure freedom on the first ASM,” said Barnard.
It’s not clear why there’s such a difference, although it may be related to a predominance in the HEP study of patients taking levetiracetam as the first-line ASM. “We didn’t directly look at the rate of treatment response or seizure freedom on levetiracetam,” which is something that will be addressed in a follow-up study, Barnard added.
The difference could be due to the study including only focal epilepsy patients, “who usually have a different treatment regime,” or it could be related to using updated definitions in this study, she said.
Results also showed that patients are at high risk during the first year of treatment, with two thirds experiencing ongoing or worsening seizures during this period. “People have ongoing seizures for the first year, even if they go on to become seizure-free,” Barnard noted.
Experiencing ongoing seizures has potential implications for driving and for employment, she added.
A self-reported history of a psychological disorder was a risk factor for increased treatment resistance. Upon enrollment, each participant completed the Mini International Neuropsychiatric Interview, which Barnard said is a diagnostic, rather than a screening, tool.
One of the team’s next research steps is to look more closely at the role of depression, anxiety, bipolar disorder, and suicidality on treatment response in this patient population, said Barnard.
Important for Patient Counseling
Commenting on the research, Patrick Kwan, MD, PhD, professor, Department of Neuroscience, Monash University, said the research is “very important” in terms of patient counseling.
“For someone newly diagnosed with epilepsy, starting the first medication can be both daunting and confusing, with many uncertainties,” said Kwan. “That’s why it’s valuable to know that nearly a third of patients may not respond to initial treatment.”
He noted that the patients in the study were recruited from major centers, which could attract a specific subset of individuals. “It’s possible that this patient population might represent more severe cases,” he explained.
Kwan also emphasized that the study did not examine the “patterns” of prescription drug choices, adding that he agreed this should be addressed in future analyses.
The researchers and Kwan reported no relevant disclosures.
A version of this article appeared on Medscape.com.
LOS ANGELES — Only about 27% of patients newly diagnosed with focal epilepsy are seizure-free on initial anti-seizure medications (ASMs), new research suggested.
This is sobering information to pass on to patients with focal epilepsy who may have high expectations based on prior data. “Patients tend to expect things to happen quickly, said study investigator Sarah Barnard, MD, a research fellow at the School of Translational Medicine, Monash University, Melbourne, Australia.
The study was presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
An International Collaboration
The study is part of the International Human Epilepsy Project (HEP), which focuses on new-onset focal epilepsy, one of the most common forms of the disorder. The researchers are aiming to identify factors that influence treatment response in this population.
For example, they will investigate how specific medications and coexisting conditions affect treatment outcomes. Ultimately, the goal is to enable the development of individualized treatment plans for patients, leading to faster and more effective improvements or potential cures for the condition.
“The investigators wanted to focus in on focal epilepsy and exclude patients with more severe phenotypes, such as those with developmental delays or significant brain injury,” said Barnard. Individuals with focal epilepsy are generally healthy, she added.
In addition, previous studies may have used differing definitions of seizure freedom, said Barnard.
The study included 448 patients, median age about 33 years and 60% women, with focal epilepsy who were enrolled at 34 tertiary epilepsy centers in the United States, Europe, and Australia within 4 months of initiating ASM treatment.
Participants were followed for up to 6 years (the median was 3.13 years). The median age at seizure onset was 29 years, and the median age of treatment initiation was 32 years. The most common first-line ASMs were levetiracetam (56.9%) and lamotrigine (16.5%).
Researchers used updated International League Against Epilepsy definitions. Seizure freedom is defined as no seizures for 12 months or three times the longest pretreatment seizure-free interval, whichever is longer.
Results showed that only 27% of patients were seizure-free in the first year after diagnosis even accounting for a 2-month “medication adjustment” period.
Managing Expectations
Although the study excluded individuals with more severe types of epilepsy, “we still identified a substantial proportion of treatment-resistant cases, suggesting that much more complex factors are at play,” said Jacqueline French, MD, a study coinvestigator and professor at the NYU Langone’s Comprehensive Epilepsy Center in New York City.
“I don’t think we adequately prepare our patients for the challenges of the first year, which can be quite turbulent,” French said.
However, the seizure freedom rate in this study is lower than previous estimates. “It’s much less than what was predicted in other studies, some of which quote around 50%-55% seizure freedom on the first ASM,” said Barnard.
It’s not clear why there’s such a difference, although it may be related to a predominance in the HEP study of patients taking levetiracetam as the first-line ASM. “We didn’t directly look at the rate of treatment response or seizure freedom on levetiracetam,” which is something that will be addressed in a follow-up study, Barnard added.
The difference could be due to the study including only focal epilepsy patients, “who usually have a different treatment regime,” or it could be related to using updated definitions in this study, she said.
Results also showed that patients are at high risk during the first year of treatment, with two thirds experiencing ongoing or worsening seizures during this period. “People have ongoing seizures for the first year, even if they go on to become seizure-free,” Barnard noted.
Experiencing ongoing seizures has potential implications for driving and for employment, she added.
A self-reported history of a psychological disorder was a risk factor for increased treatment resistance. Upon enrollment, each participant completed the Mini International Neuropsychiatric Interview, which Barnard said is a diagnostic, rather than a screening, tool.
One of the team’s next research steps is to look more closely at the role of depression, anxiety, bipolar disorder, and suicidality on treatment response in this patient population, said Barnard.
Important for Patient Counseling
Commenting on the research, Patrick Kwan, MD, PhD, professor, Department of Neuroscience, Monash University, said the research is “very important” in terms of patient counseling.
“For someone newly diagnosed with epilepsy, starting the first medication can be both daunting and confusing, with many uncertainties,” said Kwan. “That’s why it’s valuable to know that nearly a third of patients may not respond to initial treatment.”
He noted that the patients in the study were recruited from major centers, which could attract a specific subset of individuals. “It’s possible that this patient population might represent more severe cases,” he explained.
Kwan also emphasized that the study did not examine the “patterns” of prescription drug choices, adding that he agreed this should be addressed in future analyses.
The researchers and Kwan reported no relevant disclosures.
A version of this article appeared on Medscape.com.
LOS ANGELES — Only about 27% of patients newly diagnosed with focal epilepsy are seizure-free on initial anti-seizure medications (ASMs), new research suggested.
This is sobering information to pass on to patients with focal epilepsy who may have high expectations based on prior data. “Patients tend to expect things to happen quickly, said study investigator Sarah Barnard, MD, a research fellow at the School of Translational Medicine, Monash University, Melbourne, Australia.
The study was presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
An International Collaboration
The study is part of the International Human Epilepsy Project (HEP), which focuses on new-onset focal epilepsy, one of the most common forms of the disorder. The researchers are aiming to identify factors that influence treatment response in this population.
For example, they will investigate how specific medications and coexisting conditions affect treatment outcomes. Ultimately, the goal is to enable the development of individualized treatment plans for patients, leading to faster and more effective improvements or potential cures for the condition.
“The investigators wanted to focus in on focal epilepsy and exclude patients with more severe phenotypes, such as those with developmental delays or significant brain injury,” said Barnard. Individuals with focal epilepsy are generally healthy, she added.
In addition, previous studies may have used differing definitions of seizure freedom, said Barnard.
The study included 448 patients, median age about 33 years and 60% women, with focal epilepsy who were enrolled at 34 tertiary epilepsy centers in the United States, Europe, and Australia within 4 months of initiating ASM treatment.
Participants were followed for up to 6 years (the median was 3.13 years). The median age at seizure onset was 29 years, and the median age of treatment initiation was 32 years. The most common first-line ASMs were levetiracetam (56.9%) and lamotrigine (16.5%).
Researchers used updated International League Against Epilepsy definitions. Seizure freedom is defined as no seizures for 12 months or three times the longest pretreatment seizure-free interval, whichever is longer.
Results showed that only 27% of patients were seizure-free in the first year after diagnosis even accounting for a 2-month “medication adjustment” period.
Managing Expectations
Although the study excluded individuals with more severe types of epilepsy, “we still identified a substantial proportion of treatment-resistant cases, suggesting that much more complex factors are at play,” said Jacqueline French, MD, a study coinvestigator and professor at the NYU Langone’s Comprehensive Epilepsy Center in New York City.
“I don’t think we adequately prepare our patients for the challenges of the first year, which can be quite turbulent,” French said.
However, the seizure freedom rate in this study is lower than previous estimates. “It’s much less than what was predicted in other studies, some of which quote around 50%-55% seizure freedom on the first ASM,” said Barnard.
It’s not clear why there’s such a difference, although it may be related to a predominance in the HEP study of patients taking levetiracetam as the first-line ASM. “We didn’t directly look at the rate of treatment response or seizure freedom on levetiracetam,” which is something that will be addressed in a follow-up study, Barnard added.
The difference could be due to the study including only focal epilepsy patients, “who usually have a different treatment regime,” or it could be related to using updated definitions in this study, she said.
Results also showed that patients are at high risk during the first year of treatment, with two thirds experiencing ongoing or worsening seizures during this period. “People have ongoing seizures for the first year, even if they go on to become seizure-free,” Barnard noted.
Experiencing ongoing seizures has potential implications for driving and for employment, she added.
A self-reported history of a psychological disorder was a risk factor for increased treatment resistance. Upon enrollment, each participant completed the Mini International Neuropsychiatric Interview, which Barnard said is a diagnostic, rather than a screening, tool.
One of the team’s next research steps is to look more closely at the role of depression, anxiety, bipolar disorder, and suicidality on treatment response in this patient population, said Barnard.
Important for Patient Counseling
Commenting on the research, Patrick Kwan, MD, PhD, professor, Department of Neuroscience, Monash University, said the research is “very important” in terms of patient counseling.
“For someone newly diagnosed with epilepsy, starting the first medication can be both daunting and confusing, with many uncertainties,” said Kwan. “That’s why it’s valuable to know that nearly a third of patients may not respond to initial treatment.”
He noted that the patients in the study were recruited from major centers, which could attract a specific subset of individuals. “It’s possible that this patient population might represent more severe cases,” he explained.
Kwan also emphasized that the study did not examine the “patterns” of prescription drug choices, adding that he agreed this should be addressed in future analyses.
The researchers and Kwan reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AES 2024
Bariatric Surgery Better Than Obesity Drugs for Some Patients With MASLD
SAN DIEGO — , new study results showed.
In a separate analysis of data from the same study, researchers also found that bariatric surgery alone had lower risks for major adverse cardiovascular events (MACEs) than GLP-1 or SGLT2 inhibitor use or a combination of surgery and medications.
“While weight loss medications have demonstrated notable success, especially in managing diabetes and aiding weight loss, bariatric surgery offers more significant and varied benefits for weight and metabolic health, making it a better option for some patients,” said Leith Ghani, DO, an internal medicine resident at The University of Arizona College of Medicine – Phoenix.
Ghani presented the findings about mortality at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). His co-author and fellow internal medicine resident Qumber Ali, DO, presented the findings about MACEs.
These findings highlight “the need for personalized treatment plans, allowing the decision between surgery and medication to be customized according to each patient’s specific situation and health goals,” Ghani said. “It also emphasizes the importance of a multidisciplinary approach to patient management.”
Comparing Bariatric Interventions and Pharmacologic Treatments
The retrospective, multicenter study of hospital admissions data from the Banner Health system in Phoenix included more than 8600 patients who had MASLD-related diagnostic codes and metabolic criteria. Patients were divided into four groups according to the treatment they received: Bariatric surgery alone (5.8%), GLP-1 medications (39.3%), SGLT2 inhibitor medications (23.4%), or a combination of surgery and medications (31.5%).
In the mortality analysis, Ghani and colleagues looked at data for patients who died between 12 and 60 months after surgery or starting medication. They found that patients who underwent bariatric surgery had a significantly higher chance of survival at 5 years.
When compared to bariatric surgery, the adjusted hazard ratio (aHR) for GLP-1 medications was 2.99, followed by an aHR of 2.96 for SGLT2 inhibitor medications, and an aHR of 1.78 for a combination of treatments.
In the MACE analysis, Ali and colleagues looked at data for patients who were followed for 12 months or more after intervention or initiation of treatment, identifying MACE diagnostic codes for coronary artery disease, cerebrovascular disease, and congestive heart failure. They found that patients who underwent bariatric surgery alone had a significantly lower rate of MACEs.
When compared to bariatric surgery, the aHR was 1.83 for GLP-1 medications, 1.72 for SGLT2 inhibitor medications, and 1.91 for a combination of treatments.
Regarding both analyses, patients taking GLP-1 or SGLT2 inhibitor medications may face higher risks for mortality or serious heart problems due to existing metabolic disorders or heart disease, Ali said.
Future studies could look at other risk factors that make these patients more vulnerable, he added. For instance, factors related to body mass index, glucose control, other medications, different clinical settings, and race/ethnicity can contribute to different treatment responses, as could the decision to take medication or undergo surgery in the first place.
“This emphasizes the need for additional, prospective randomized clinical trial research to explore why these differences exist,” Ali said. “While progress has been made, there is still much to learn about the optimal management of patients with metabolic and cardiovascular disorders.”
Considering a Multidisciplinary Approach to MASLD Treatment
Ghani and Ali also called for personalized treatment plans for metabolic-related disorders such as MASLD, as well as strong communication among specialists and with patients about the benefits and risks of choosing certain medications and procedures.
“Bariatric surgery is not a universal solution, and not all patients are suitable for surgery,” Ghani said. “We also can’t say at this point that drug treatments are worse than bariatric surgery. The effectiveness of these therapies can vary greatly depending on a patient’s health, lifestyle, and preferences.”
Looking ahead, MASLD studies should investigate long-term weight loss seen with bariatric surgery and different medications, said Katherine Schwenger, PhD, RD, a scientific associate at Toronto General Hospital in Toronto, Ontario, Canada.
“GLP-1s are a hot topic right now,” said Schwenger, who wasn’t involved with the study. But “we need to look at factors such as the longevity of weight loss. It’s hard to beat the success and sustainability of bariatric surgery.”
Ghani, Ali, and Schwenger reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO — , new study results showed.
In a separate analysis of data from the same study, researchers also found that bariatric surgery alone had lower risks for major adverse cardiovascular events (MACEs) than GLP-1 or SGLT2 inhibitor use or a combination of surgery and medications.
“While weight loss medications have demonstrated notable success, especially in managing diabetes and aiding weight loss, bariatric surgery offers more significant and varied benefits for weight and metabolic health, making it a better option for some patients,” said Leith Ghani, DO, an internal medicine resident at The University of Arizona College of Medicine – Phoenix.
Ghani presented the findings about mortality at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). His co-author and fellow internal medicine resident Qumber Ali, DO, presented the findings about MACEs.
These findings highlight “the need for personalized treatment plans, allowing the decision between surgery and medication to be customized according to each patient’s specific situation and health goals,” Ghani said. “It also emphasizes the importance of a multidisciplinary approach to patient management.”
Comparing Bariatric Interventions and Pharmacologic Treatments
The retrospective, multicenter study of hospital admissions data from the Banner Health system in Phoenix included more than 8600 patients who had MASLD-related diagnostic codes and metabolic criteria. Patients were divided into four groups according to the treatment they received: Bariatric surgery alone (5.8%), GLP-1 medications (39.3%), SGLT2 inhibitor medications (23.4%), or a combination of surgery and medications (31.5%).
In the mortality analysis, Ghani and colleagues looked at data for patients who died between 12 and 60 months after surgery or starting medication. They found that patients who underwent bariatric surgery had a significantly higher chance of survival at 5 years.
When compared to bariatric surgery, the adjusted hazard ratio (aHR) for GLP-1 medications was 2.99, followed by an aHR of 2.96 for SGLT2 inhibitor medications, and an aHR of 1.78 for a combination of treatments.
In the MACE analysis, Ali and colleagues looked at data for patients who were followed for 12 months or more after intervention or initiation of treatment, identifying MACE diagnostic codes for coronary artery disease, cerebrovascular disease, and congestive heart failure. They found that patients who underwent bariatric surgery alone had a significantly lower rate of MACEs.
When compared to bariatric surgery, the aHR was 1.83 for GLP-1 medications, 1.72 for SGLT2 inhibitor medications, and 1.91 for a combination of treatments.
Regarding both analyses, patients taking GLP-1 or SGLT2 inhibitor medications may face higher risks for mortality or serious heart problems due to existing metabolic disorders or heart disease, Ali said.
Future studies could look at other risk factors that make these patients more vulnerable, he added. For instance, factors related to body mass index, glucose control, other medications, different clinical settings, and race/ethnicity can contribute to different treatment responses, as could the decision to take medication or undergo surgery in the first place.
“This emphasizes the need for additional, prospective randomized clinical trial research to explore why these differences exist,” Ali said. “While progress has been made, there is still much to learn about the optimal management of patients with metabolic and cardiovascular disorders.”
Considering a Multidisciplinary Approach to MASLD Treatment
Ghani and Ali also called for personalized treatment plans for metabolic-related disorders such as MASLD, as well as strong communication among specialists and with patients about the benefits and risks of choosing certain medications and procedures.
“Bariatric surgery is not a universal solution, and not all patients are suitable for surgery,” Ghani said. “We also can’t say at this point that drug treatments are worse than bariatric surgery. The effectiveness of these therapies can vary greatly depending on a patient’s health, lifestyle, and preferences.”
Looking ahead, MASLD studies should investigate long-term weight loss seen with bariatric surgery and different medications, said Katherine Schwenger, PhD, RD, a scientific associate at Toronto General Hospital in Toronto, Ontario, Canada.
“GLP-1s are a hot topic right now,” said Schwenger, who wasn’t involved with the study. But “we need to look at factors such as the longevity of weight loss. It’s hard to beat the success and sustainability of bariatric surgery.”
Ghani, Ali, and Schwenger reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO — , new study results showed.
In a separate analysis of data from the same study, researchers also found that bariatric surgery alone had lower risks for major adverse cardiovascular events (MACEs) than GLP-1 or SGLT2 inhibitor use or a combination of surgery and medications.
“While weight loss medications have demonstrated notable success, especially in managing diabetes and aiding weight loss, bariatric surgery offers more significant and varied benefits for weight and metabolic health, making it a better option for some patients,” said Leith Ghani, DO, an internal medicine resident at The University of Arizona College of Medicine – Phoenix.
Ghani presented the findings about mortality at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). His co-author and fellow internal medicine resident Qumber Ali, DO, presented the findings about MACEs.
These findings highlight “the need for personalized treatment plans, allowing the decision between surgery and medication to be customized according to each patient’s specific situation and health goals,” Ghani said. “It also emphasizes the importance of a multidisciplinary approach to patient management.”
Comparing Bariatric Interventions and Pharmacologic Treatments
The retrospective, multicenter study of hospital admissions data from the Banner Health system in Phoenix included more than 8600 patients who had MASLD-related diagnostic codes and metabolic criteria. Patients were divided into four groups according to the treatment they received: Bariatric surgery alone (5.8%), GLP-1 medications (39.3%), SGLT2 inhibitor medications (23.4%), or a combination of surgery and medications (31.5%).
In the mortality analysis, Ghani and colleagues looked at data for patients who died between 12 and 60 months after surgery or starting medication. They found that patients who underwent bariatric surgery had a significantly higher chance of survival at 5 years.
When compared to bariatric surgery, the adjusted hazard ratio (aHR) for GLP-1 medications was 2.99, followed by an aHR of 2.96 for SGLT2 inhibitor medications, and an aHR of 1.78 for a combination of treatments.
In the MACE analysis, Ali and colleagues looked at data for patients who were followed for 12 months or more after intervention or initiation of treatment, identifying MACE diagnostic codes for coronary artery disease, cerebrovascular disease, and congestive heart failure. They found that patients who underwent bariatric surgery alone had a significantly lower rate of MACEs.
When compared to bariatric surgery, the aHR was 1.83 for GLP-1 medications, 1.72 for SGLT2 inhibitor medications, and 1.91 for a combination of treatments.
Regarding both analyses, patients taking GLP-1 or SGLT2 inhibitor medications may face higher risks for mortality or serious heart problems due to existing metabolic disorders or heart disease, Ali said.
Future studies could look at other risk factors that make these patients more vulnerable, he added. For instance, factors related to body mass index, glucose control, other medications, different clinical settings, and race/ethnicity can contribute to different treatment responses, as could the decision to take medication or undergo surgery in the first place.
“This emphasizes the need for additional, prospective randomized clinical trial research to explore why these differences exist,” Ali said. “While progress has been made, there is still much to learn about the optimal management of patients with metabolic and cardiovascular disorders.”
Considering a Multidisciplinary Approach to MASLD Treatment
Ghani and Ali also called for personalized treatment plans for metabolic-related disorders such as MASLD, as well as strong communication among specialists and with patients about the benefits and risks of choosing certain medications and procedures.
“Bariatric surgery is not a universal solution, and not all patients are suitable for surgery,” Ghani said. “We also can’t say at this point that drug treatments are worse than bariatric surgery. The effectiveness of these therapies can vary greatly depending on a patient’s health, lifestyle, and preferences.”
Looking ahead, MASLD studies should investigate long-term weight loss seen with bariatric surgery and different medications, said Katherine Schwenger, PhD, RD, a scientific associate at Toronto General Hospital in Toronto, Ontario, Canada.
“GLP-1s are a hot topic right now,” said Schwenger, who wasn’t involved with the study. But “we need to look at factors such as the longevity of weight loss. It’s hard to beat the success and sustainability of bariatric surgery.”
Ghani, Ali, and Schwenger reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM AASLD 2024
Do Risk-Reducing Surgeries Benefit BRCA Carriers With Early-Onset Breast Cancer History?
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SABCS 2024