Abstract
BACKGROUND: Patients with lower-risk myelodysplastic syndromes (MDS) may experience anemia and a high transfusion burden, alongside a risk of progression to acute myeloid leukemia. Luspatercept, a recombinant fusion protein that acts as an erythroid maturation agent, was FDA/EMA-approved in 2020 based on the phase III MEDALIST trial. There remains an unmet need for anemia treatment in Asian patients for whom red blood cell (RBC) transfusion is a standard of care, and in whom rates/severity of anemia and serum erythropoietin levels are often higher versus Western patients. OBJECTIVES: The objective of this study was to assess the efficacy, safety, and tolerability of luspatercept in Asian patients with anemia due to transfusion-dependent lower-risk MDS with ring sideroblasts. DESIGN: This was a phase II, single-arm, interventional bridging study (NCT04477850). METHODS: Patients from China and Japan with very low-, low-, or intermediate-risk MDS with ring sideroblasts who were RBC transfusion-dependent received subcutaneous luspatercept starting at 1.0 mg/kg every 3 weeks. The primary endpoint was RBC transfusion independence (TI) ⩾8 weeks (weeks 1-24). RESULTS: There was a statistically significant, clinically meaningful improvement of anemia in Asian patients; 60% (n = 18, p < 0.0001) achieved RBC-TI for ⩾8 weeks and 43% (n = 13) for ⩾12 weeks (weeks 1-24). Safety was consistent with the known profile of luspatercept in MDS. CONCLUSION: These results support luspatercept as a well-tolerated, efficacious alternative to transfusions for Asian patients with lower-risk MDS, who tend to have more severe anemia. Trial registration: clinicaltrials.gov, NCT04477850.