A longitudinal analysis of data from the phase III BELIEVE trial showed that treatment with the activin receptor ligand trap luspatercept was associated with sustained reductions in red blood cell transfusion (RBC) units and fewer transfusion visits in patients with beta thalassemia. These results were presented by Ali T. Taher, MD, PhD, FRCP, of the American University of Beirut, as part of the 2020 ASH Annual Meeting.
"Beta thalassemia is a genetic blood disorder characterized by ineffective erythropoiesis and anemia," Dr. Taher explained. "There is a clinical need to reduce transfusions and iron burden in patients with anemia due to beta thalassemia." Luspatercept was approved by the FDA for treatment of thalassemia in 2019.
The 336 patients with transfusion-dependent beta thalassemia who were enrolled in the BELIEVE trial were randomized to receive either luspatercept at a starting dose of 1.0 mg/kg (n=224) or placebo (n=112) subcutaneously every three weeks for at least 48 weeks. In both treatment arms, patients received supportive care, including RBC transfusions to maintain target Hb levels and iron chelation therapy. After study unblinding, participants receiving placebo were able to switch to luspatercept.
Response to luspatercept was defined as achieving â‰¥33% reduction in RBC transfusion burden during weeks 13-24, with a reduction of â‰¥2 RBC transfusion units from baseline. Changes in RBC transfusion burden and visits were assessed at every 24 weeks from treatment initiation until data cutoff on July 1, 2019.
During weeks one to 24 of treatment, patients receiving luspatercept group experienced a mean change in RBC units of –2.20, compared with +0.72 units over the same period in the placebo arm. That trend continued during the study: From week 25 to 48, the mean change in RBC units was –2.3 for luspatercept-treated patients and +0.21 for patients in the placebo group.
As expected, the reduction was greatest in patients who responded to luspatercept treatment. The mean reduction in transfusion units was –5.32 in –4.83 units per 24-week period during weeks 1 to 24 and 25 to 48, respectively, in responders, compared with –1.30 and –1.85, respectively, in nonresponders.
Participants receiving luspatercept also had fewer transfusion visits during the first 48 weeks of the study (negative values indicate fewer visits compared to baseline transfusion visit rate, positive values indicate more visits):
- weeks 1-24: –0.49 vs. in the luspatercept group vs. +0.32 in the placebo group
- weeks 25-48: –0.54 vs. +0.14
Commenting on patients who had longer-term follow-up, Dr. Taher noted that "luspatercept-treated patients continued to experience durable, sustained reductions in RBC units and transfusion visits up to 144 weeks of follow-up." (See TABLE for data about long-term response.) However, "as the BELIEVE trial is still ongoing, only a small number of patients could be evaluated at later time points," he added.
Study authors report relationships with Acceleron, which sponsored the trial.
Taher AT, Viprakasit V, Hermine O, et al. Sustained reductions in red blood cell (RBC) transfusion burden and events in Î²-thalassemia with luspatercept: longitudinal results of the BELIEVE trial. Abstract #1695. Presented at the 2020 American Society of Hematology Annual Meeting, December 6, 2020.