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.
Singh et al. (Thu,) studied this question.