Outcomes with luspatercept in patients with β-thalassemia: a systematic review and meta-analysis

Abstract

β-thalassaemia is a genetic blood disorder characterized by ineffective erythropoiesis and chronic anaemia, often requiring lifelong red blood cell (RBC) transfusions. Luspatercept, an erythroid maturation agent, has emerged as a potential therapy to reduce transfusion burden in affected adults. To assess the clinical efficacy and safety of luspatercept in managing adult patients with β-thalassemia. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating luspatercept in adult patients with β-thalassemia. A comprehensive search of PubMed, Scopus, Embase, Cochrane Library, and ClinicalTrials.gov was performed for studies published up to May 2025. Only English-language RCTs were included. Data were extracted on transfusion burden, hemoglobin response, and adverse events. Risk of bias was assessed using the Cochrane ROB 2 tool. Pooled estimates were calculated using a random-effects model with the Freeman-Tukey double arcsine transformation. Heterogeneity was assessed using the I² statistic. Out of 587 identified records, three RCTs and one single-arm trial (n = 608 patients) met the inclusion criteria. Of these, 447 patients received luspatercept and 161 received placebo. Luspatercept was associated with a ≥ 33% reduction in RBC transfusion burden in 58% (95% CI: 0.33-0.79) and a ≥ 50% reduction in 40% (95% CI: 0.25-0.58) of patients. Transfusion independence was achieved in 36% (95% CI: 0.13-0.69). Common adverse events included headache (32%), bone pain (33%), arthralgia (22%), and back pain (20%). Grade ≥ 3 adverse events occurred in 21% (95% CI: 0.09-0.41). Overall, luspatercept effectively reduced transfusion needs with an acceptable safety profile. Luspatercept significantly reduces transfusion burden in patients with β-thalassemia and demonstrates a manageable safety profile. These findings support luspatercept as an effective and well-tolerated therapeutic option that meaningfully reduces transfusion burden, potentially decreasing iron overload and improving quality of life for patients with β-thalassemia.