According to the results of a study published in The New England Journal of Medicine, luspatercept, a first-in-class erythroid maturation agent, increased the percentage of patients with transfusion-dependent beta-thalassemia who had a reduction in transfusion burden relative to the group of patients that received placebo.

M. Domenica Cappellini, MD, of the Department of Clinical Sciences and Community, University of Milan, IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital in Italy, and colleagues conducted BELIEVE ( Identifier: NCT02604433), a randomized, double-blind, phase 3 trial, to determine the efficacy and safety of luspatercept plus best supportive care (BSC) compared with placebo plus BSC in adults with transfusion-dependent beta-thalassemia. From July 2016 to June 2017, patients were randomly assigned (2:1) to receive BSC plus luspatercept (1.00-1.25 mg/kilogram of body weight) or placebo for a minimum of 48 weeks.

The primary end point was the percentage of patients who had a reduction in the transfusion burden (≥ 33% from baseline) and a reduction in red-cell units (≥ 2 units) over a 12-week interval from weeks 13 to 24. Secondary outcomes measures included a reduction in the transfusion burden during any 12-week interval and changes in serum ferritin levels.

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A total of 336 patients (224 patients received luspatercept; 112 patients received placebo) participated in the study. The median age of participants was 30 years and 58% of participants were female. The treatments were administered for a median of 64 weeks in both groups (luspatercept range, 3 – 97 weeks; placebo range 9 – 92).

During the 12-week interval for the primary endpoint, the percentage of patients who had a reduction in transfusion burden and in red-cell units was higher in the luspatercept group compared with the placebo group (21.4% vs 4.5%; P <.001).

During any 12-week interval for the secondary outcomes, the percentage of patients who had a reduction in transfusion burden was higher in the luspatercept group compared with the placebo group (70.5% vs 29.5%; odds ratio, 5.69; 95% CI: 3.46 – 9.35).

For the secondary endpoint of mean change from baseline in serum ferritin level, the least-squares mean difference between the groups after 48 weeks was −348 μg/L (95% CI: −517 to −179) in favor of luspatercept (mean change [±SD], −248 ± 800 μg/L) over the placebo (mean change [±SD], 107 ± 526 μg/L).

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Most patients in both groups had at least 1 adverse event (luspatercept, 96.0%; 95% CI: 92.5 – 98.1 and placebo, 92.7%; 95% CI: 86.0 – 96.8). Common adverse events (in at least 5% of patients in the luspatercept group) that showed an increased incidence (of at least 5% greater) in the luspatercept group relative to the placebo group included transient bone pain (19.7% vs 8.3%), arthralgia (19.3% vs 11.9%), dizziness (11.2% vs 4.6%), hypertension (8.1% vs 2.8%), and hyperuricemia (7.2% vs. 0%).

“The response with luspatercept was sustained, and multiple episodes of response were observed,” wrote the authors. “A 5-year open-label extension phase is under way to provide long-term data on the safety of luspatercept and its effects on the transfusion burden and iron outcomes.”

Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


  1. Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219-1231.