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.

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.

Reference

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