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

Abstract Background β-thalassaemia is a genetic blood disorder marked 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 the transfusion burden in affected patients. This study aims to assess the outcomes with luspatercept in patients with β-thalassemia. Methods Following PRISMA guidelines, a comprehensive search of PubMed, Cochrane, Embase, Google Scholar, and ClinicalTrials.gov (inception to May 2025) was conducted using MeSH terms for “ β-thalassaemia” and ”luspatercept.” After screening and excluding review articles, meta-analyses, and studies without a patient population of interest, four studies reporting the outcomes of luspatercept in patients with β-thalassemiawere selected for inclusion from a total of 587 references. Some characteristics were described systematically. Pooled estimates were calculated using a random-effects model, and heterogeneity was assessed using the I² statistic. Results A total of 447 patients from three Phase II and one Phase III trials were included for analysis and review. The median age was 38,25 years (range, 18-66), 56% (n = 249/447) were females. The pooled rate for transfusion independence was 36% (95% CI 0.13-0.69, I2 90.4%, p < 0.0001). The pooled rates for reduction in transfusion burden by >33% and >50% were 58% (95% CI 0.33-0.79, I2 92%%, p < 0.0001) and 40% (95% CI 0.25-0.58, I2 83.3%, p + 0.0004), respectively. The pooled rate for mean increase in serum haemoglobin by >1 g/dL was 69% (95% CI 0.53-0.81, I2 66.9%, p = 0.0488). The pooled rate for grade 3 or above adverse events was 21% (95% CI 0.09-0.41, I2 92.9%%, p < 0.0001). The pooled rates for pyrexia, headache, and nausea were 14% (95% CI 0.07-0.25, I2 76.7%, p = 0.0137), 32% (95% CI 0.28-0.37, I2 0.0 %, p = 0.4771), and 10% (95% CI 0.06-0.17, I2 54.2%, p = 0.1127), respectively. The pooled rate for arthralgias, asthenia, and injection site adverse events were 23% (95% CI 0.19-0.28, I2 9.9%, p = 0.3435), 12% (95% CI 0.09-0.16, I2 0.0%, p = 0.8251), and 8% (95% CI 0.0.05-0.13, I2 56.4%, p = 0.0758), respectively. Conclusion Luspatercept significantly reduces the transfusion burden in patients with β-thalassemia and demonstrates a favourable safety profile. This study supports the use of luspatercept as an effective and well-tolerated therapeutic option for β-thalassemia while highlighting the need for continued research to consolidate these findings.