BELIEVE Trial: Luspatercept Reduces Transfusion Burden in β-Thalassemia

β-thalassemia is a blood disorder that reduces the production of hemoglobin. It is an inherited hemoglobinopathy associated with an erythroid maturation defect characterized by ineffective erythropoiesis and impaired maturation of red blood cells (RBCs). In people with β–thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body.

Luspatercept is a new agent under development to treat β-thalassemia. At the ASH annual meeting, a group of international researchers from the BELIEVE trial, a phase III, randomized, double-blind, placebo-controlled study, presented data showing that treatment with luspatercept led to significant reductions in RBC transfusion burden in adults with transfusion-dependent β-thalassemia. Lead author Maria Domenica Cappellini, MD, of Milan, Italy, collaborated with an international team of coauthors.

The study enrolled, randomized, and treated 336 patients who were 18 years or older, had β-thalassemia or hemoglobin (Hb) E/β‑thalassemia, required regular transfusions of 6–20 RBC units in the 24 weeks prior to randomization, and had no transfusion-free period of 35 days or longer during those 24 weeks. The sample’s median age was 30 years (range 18–66), and 58% of patients were female.

The researchers randomized subjects (2:1) to receive luspatercept or placebo every three weeks for at least 48 weeks. Patients in both treatment arms continued to receive RBC transfusions and iron chelation therapy. The primary endpoint was a reduction in transfusion burden of 33% or more during weeks 13–24, as compared to the 12-week baseline.

In the luspatercept group, 48 of 224 (21.4%) patients reached the primary endpoint; in the placebo group, 5 of 112 (4.5%) did so. At weeks 37–48, 44 of 224 (19.6%) patients receiving luspatercept achieved a 33% or better reduction in RBC transfusion burden, compared with 4 of 112 (3.6%) patients receiving placebo. The researchers also evaluated a 50% or better reduction in RBC transfusion burden at 13–24 and 37–48 weeks. They found that patients receiving luspatercept had rates of 7.6% and 10.3%, compared with 1.8% and 0.9% of those on placebo, respectively.

Patients experienced adverse events similar to those reported in the phase II trial, and treatment-emergent adverse events that led to dose delays or reductions were similar between both groups. No deaths occurred among patients receiving luspatercept.

The authors concluded that treatment with luspatercept significantly reduced RBC transfusion burden in adults with transfusion-dependent β-thalassemia, observing that luspatercept was well tolerated in their patient population.