| Beta-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. This study aim was to determine whether luspatercept could improve anemia and disease complications in patients with beta-thalassemia. This open-label, nonrandomized, uncontrolled study (NCT01749540 and NCT02268409) consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5 year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non-transfusion-dependent (mean hemoglobin <10.0 g/dL and <4 red blood cell [RBC] units transfused/8 weeks) and 31 were transfusion-dependent (≥4 RBC units/8 weeks). Patients received 0.2-1.25 mg/kg luspatercept subcutaneously every 21 days for ≥5 cycles in the dose-finding stage, and 0.8-1.25 mg/kg in an expansion cohort and 5-year extension. The primary endpoint was erythroid response, defined as hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 consecutive days (with no RBC transfusions) for non-transfusion-dependent patients, or reduction in RBC transfusion burden of ≥20% over a 12-week period versus the 12 weeks before treatment for transfusion-dependent patients. Eighteen (58%) non-transfusion-dependent patients receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase ≥1.5 g/dL over ≥14 days versus baseline. Twenty-six (81%) with transfusion dependence achieved ≥20% reduction in RBC transfusion burden. The most common grade 1-2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of beta-thalassemia patients receiving luspatercept had improvements in hemoglobin or transfusion burden. These findings support a randomized clinical trial to assess efficacy and safety. |
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