Luspatercept for Lower-Risk Myelodysplasia with Ring Sideroblasts

Erythropoietin stimulating agents (ESAs) are a standard of care for patients with lower-risk myelodysplastic syndromes (MDS). However, transfusion-dependent patients or those with increased erythropoietin levels are often refractory to ESAs. Additional options can include supportive transfusions, lenalidomide, or hypomethylating agents, although efficacy is modest, and each has safety concerns. Therefore, additional therapies are needed.

Luspatercept binds TGF-β superfamily ligands to decrease signaling by SMAD2 and SMAD3, which inhibit red cell maturation. In a prior phase II study, luspatercept resulted in erythroid responses in 63% of patients with lower-risk MDS, especially among those with ring sideroblasts (Lancet Oncol 2017; 18:1338).…