Luspatercept, a novel recombinant fusion protein that targets specific transforming growth factor (TGF)-beta proteins involved in late-stage red blood cell maturation, may lead to improvements in hemoglobin levels and transfusion burden in patients with beta thalassemia, according to a study published in Blood.

Researchers conducted an open label, nonrandomized, uncontrolled, phase 2 study with 64 patients with beta thalassemia (33 nontransfusion-dependent; 31 transfusion-dependent). In the dose-finding stage of the study, patients received 0.2 mg/kg to 1.25 mg/kg luspatercept subcutaneously every 21 days for up to 5 cycles. Based on the results from that stage, patients received 0.8 mg/kg to 1.25 mg/kg luspatercept in an expansion cohort and 5-year extension stage.

The primary endpoint was erythroid response, defined as a hemoglobin increase from baseline of at least 1.5 g/dL for at least 2 weeks in nontransfusion-dependent patients and a 20% or greater reduction in red blood cell transfusion burden in transfusion-dependent patients. The researchers found that 18 (58%) nontransfusion-dependent patients receiving higher dosages of luspatercept (0.6 mg/kg-1.25 mg/kg) and 26 (81%) transfusion-dependent patients met the primary endpoint.

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The most common grade 1 or 2 adverse events were bone pain, headache, and myalgia. Quality of life was found to correlate with change in hemoglobin levels (P =.002) in nontransfusion-dependent patients.

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The researchers concluded that 1.0 mg/kg luspatercept may be an appropriate starting dose for patients with beta thalassemia, with titration up to 1.25 mg/kg. They noted that a randomized clinical trial to assess efficacy and safety of luspatercept was warranted.


1. Piga A, Perrotta S, Gamberini MR, et al. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia [published online January 7, 2019]. Blood. doi: 10.1182/blood-2018-10-879247