Luspatercept safe, effective in nontransfusion-dependent beta-thalassemia
Click Here to Manage Email Alerts
Luspatercept appeared safe and effective at improving anemia among adults with nontransfusion-dependent beta-thalassemia, according to study results presented during the European Hematology Association 2021 Virtual Congress.
“The main pathology in patients with nontransfusion-dependent beta-thalassemia is chronic anemia, which has been linked to a greater risk for morbidity and poor quality of life,” Ali T. Taher, MD, PhD, FRCP, professor of medicine in the department of hematology and oncology and director of the Naef K. Basile Cancer Institute at American University of Beirut Medical Center and adjunct professor of hematology and medical oncology at Emory School of Medicine, told Healio. “Unfortunately, we currently do not have any approved therapy for the treatment of anemia in nontransfusion-dependent beta-thalassemia. There were some studies on older agents such as hydroxyurea, but results have been inconsistent. We now have a new agent that showed benefit in improving anemia in nontransfusion-dependent beta-thalassemia. With the rising body of evidence on the detrimental impact of anemia in these patients, this presents a landmark achievement for a patient population who did not have many treatment options.”
Luspatercept (Reblozyl; Bristol Myers Squibb, Acceleron) is an erythroid maturation agent that has been approved to treat anemia among certain adults with lower-risk myelodysplastic syndrome.
The randomized, double-blind, multicenter, phase 2 BEYOND study included 145 adults (median age, 40 years; 41.7% men; baseline median hemoglobin, 8.2 g/dL) with nontransfusion-dependent beta thalassemia. Taher and colleagues randomly assigned patients to luspatercept dosed at 1 mg/kg with titration up to 1.25 mg/kg (n = 96) or subcutaneous placebo (n = 49) every 3 weeks for at least 48 weeks. All patients continued to receive red blood cell transfusions and iron chelation therapy as best supportive care.
Achievement of at least a 1 g/dL mean hemoglobin increase from baseline during a continuous 12-week interval from weeks 13 to 24 without red blood cell transfusions served as the primary endpoint. Secondary endpoints included the proportion of patients who remained transfusion free during weeks 1 to 24, who achieved a mean hemoglobin increase of at least 1.5 g/dL from baseline to weeks 13 to 24, and who had a mean change in nontransfusion-dependent beta-thalassemia patient-reported outcome tiredness and weakness domain scores.
Result showed 77% of patients assigned luspatercept achieved a mean hemoglobin increase of at least 1 g/dL vs. no patients assigned placebo (P < .0001). Those who achieved the primary endpoint in the luspatercept group included 72.7% of patients (n = 40 of 55) who had a mean baseline hemoglobin of less than 8.5 g/dL and 82.9% of patients (n = 34 of 41) who had a mean baseline hemoglobin of at least 8.5 g/dL (P < .0001 for both).
In addition, 52.1% of patients assigned luspatercept achieved a mean hemoglobin increase of at least 1.5 g/dL during weeks 13 to 24 vs. none with placebo (P < .0001).
Most patients (89.6%) assigned luspatercept remained transfusion free at weeks 1 to 24 compared with no patients assigned placebo (P = .0013).
Researchers also observed improvements in patient-reported quality-of-life outcomes, such as tiredness and weakness, associated with hemoglobin increases, Taher said.
Grade 3 or greater treatment-emergent adverse events occurred among 28.1% of patients in the luspatercept group and 24.5% of patients in the placebo group. No deaths, malignancies or thromboembolic events were reported with luspatercept.
“We will continue to monitor efficacy and safety of luspatercept in nontransfusion-dependent beta-thalassemia long-term,” Taher said. “This is especially important for such benefits as the decrease in iron overload burden and reduced morbidity rates, which take time to manifest.”
Collapse
Taher AT, et al. Abstract S101. Presented at: European Hematology Association 2021 Virtual Congress; June 9-17, 2021.
Click Here to Manage Email Alerts