Luspatercept for myelodysplastic syndromes/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis

Luspatercept is a first-in-class erythroid maturation agent that binds several transforming growth factor-β superfamily ligands, enhancing late-stage erythropoiesis [9]. The results of the phase 3 MEDALIST study (NCT02631070) [10] led to its approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of anemia in adults with lower-risk MDS-RS or MDS/MPN-RS-T requiring ≥2 RBC units/8 weeks after erythropoiesis-stimulating agent (ESA) failure [11]. Here, we report a post hoc analysis of luspatercept efficacy and safety in patients with MDS/MPN-RS-T from the MEDALIST study. The MEDALIST study enrolled 229 adults with lower-risk MDS-RS who required ≥2 RBC units/8 weeks and were refractory or intolerant to ESAs [10]. Patients were randomized 2:1 to luspatercept or placebo, administered subcutaneously every 3 weeks for 24 weeks. Luspatercept starting dose was 1.0 mg/kg, with titration to a maximum of 1.75 mg/kg, according to transfusion requirements and adverse events [10]. The diagnosis of patients with MDS/MPN-RS-T in the intention-to-treat population was performed using cytomorphologic, cytogenetic, and molecular genetic results and blood counts. Of the 229 patients in MEDALIST study, 23 (10.0%) had MDS/MPN-RS-T; 14 were randomized to luspatercept and 9 to placebo. Baseline characteristics that differed between the two arms included lower median leukocyte count (4.8 vs 7.5 × 109/dL) and serum ferritin (1062 vs 1460 µg/dL), and higher serum erythropoietin (sEPO) (71.9 vs 54.0 U/L) (Fig. 1A). Median (range) follow-up times were 27.4 (3.5–35.6) and 13.8 (3.3–32.2) months in the luspatercept and placebo arms, respectively.