Experience with Luspatercept in SF3B1-mutant Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders marked by ineffective hematopoiesis and cytopenias. SF3B1-mutated MDS, now classified as MDS with low blasts and SF3B1 mutation (MDS-SF3B1) in the 2025 World Health Organization update, represents a distinct subtype commonly associated with ring sideroblasts (RS) and anemia. Luspatercept, a recombinant fusion protein that promotes late-stage erythropoiesis via transforming growth factor-beta pathway modulation, has shown benefit in reducing transfusion dependence in lower-risk MDS (LR-MDS)-RS. We report a case series of four patients with MDS-SF3B1 treated with luspatercept (1 mg/kg subcutaneously every 3 weeks), evaluating hematologic improvement (HI), transfusion independence (TI), and tolerability. The median age was 73 years (range: 39–84), with a male predominance (75%). All patients presented with anemia and dyserythropoiesis, and three exhibited RS. The median treatment duration was seven cycles. HI per IWG-2006 criteria was achieved in 75% of patients, and 50% attained TI. Treatment response was not assessable in one patient due to COVID-19–related mortality. Luspatercept was well tolerated, with no Grade ≥ II adverse events. Overall, luspatercept demonstrated favorable efficacy and safety in Indian patients with SF3B1-mutated LR-MDS, highlighting its value in reducing transfusion burden and improving hematologic parameters. Optimal patient selection, attention to comorbidities, and timely initiation may further enhance outcomes.