MDS-279: Efficacy and Safety of Luspatercept in Patients with Anemia: A Systematic Review

Abstract

Context: Luspatercept is an erythroid maturation agent that has been shown to improve anemia by influencing late-onset erythropoiesis. Objective: To determine safety and efficacy of luspatercept in patients aged >18 years of age and diagnosed with either myelodysplastic syndrome or beta-thalassemia. Design: Systematic review. Methods: A literature search was performed on PubMed, Embase, clinicaltrials.gov, Web of Science, and Cochrane using the MeSH terms “anemia” and “Immunoglobulin fc fragments” from database inception until 4/20/2021. After screening 420 articles, 2 randomized clinical trials (RCT, N=565) and 2 phase II trials (N=122) were included. Results: In 4 clinical trials (N=687), subcutaneous luspatercept (0.125 mg/dl to 1.75 mg/dl) was administered every 21 days for at least 48 weeks or 5 cycles to treat anemia in beta-thalassemia (N=288) and MDS (N=211) patients. The median pre-transfusion hemoglobin level was 7.6 g/dl in MDS patients and 10 g/dl in beta-thalassemia patients. Median red cell transfusion burden varied between 14 RBC units/24 weeks to 8 RBC units/8 weeks. Cappellini et al. and Piga et al. (N=400) showed >33% reduction in RBC transfusion burden in 71% (n=159/224) of patients (vs 29.5% with placebo) and >20% reduction in 80% (n=51/64) of patients with beta-thalassemia. Platzbecker et al. and Fenaux et al. (N=287) showed more than 4 RBC unit reduction/8 weeks in 47% (n=100/211) of patients with MDS treated with luspatercept (vs 21% with placebo). High-dose-treated patients had a mean increase in Hb ranging from 0.36 g/dl to 1.52 g/dl. The most common side effects included headache, back pain, bone pain, fatigue, and diarrhea in 19.6% (n=98), 19.4% (n=97), 13% (n=65), 9% (n=45), and 7.4% (n=37), respectively. More than grade 3 adverse effects were bone pains, hyperuricemia, and back pain in 6.4% (n=32), 1.2% (n=6), and 0.6% (n=3), respectively. Conclusion: Luspatercept showed better efficacy than placebo in beta-thalassemia and MDS patients to treat anemia and was well-tolerated by these patients. High-dose luspatercept has shown promising results in terms of erythroid response, measured as either a reduction in transfusion burden or a mean increase in hemoglobin levels. A number of clinical trials are ongoing to assess its efficacy in myelofibrotic disorders to further extend its usage.