In the phase III MEDALIST trial reported in The New England Journal of Medicine, Fenaux et al found that luspatercept significantly reduced the severity of anemia vs placebo in red blood cell transfusion–dependent patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts.
The double-blind trial included 229 patients from 65 sites in 11 countries with very low–, low-, or intermediate-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red blood cell transfusions. Patients were randomly assigned 2:1 between March 2016 and June 2017 to receive luspatercept at 1.0–1.75 mg/kg (n = 153) or placebo (n = 76) subcutaneously every 3 weeks. Eligible patients had disease refractory to or unlikely to respond to erythropoiesis-stimulating agents or had discontinued such agents due to adverse events. The primary endpoint was transfusion independence for 8 weeks or longer during weeks 1 through 24.
Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group vs 13% of patients in the placebo group (P < .001).
The key secondary endpoint of transfusion independence for 12 weeks or longer during both weeks 1 through 24 and weeks 1 through 48 was met by 28% vs 8% of patients for weeks 1 through 24 (P < .001) and by 33% vs 12% for weeks 1 through 48 (P < .001).
The most common adverse events of any grade observed in the luspatercept group were fatigue (27% vs 13% in the placebo group), diarrhea (22% vs 9%), asthenia (20% vs 12%), nausea (20% vs 8%), dizziness (20% vs 5%), and back pain (19% vs 7%). Grade 3 adverse events occurred in 42% vs 45% of patients, with the most common in the luspatercept group being fatigue (5%). No grade 4 adverse events were reported. Serious adverse events were reported in 31% vs 30% of patients.
The investigators concluded, “Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red [blood] cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event.”
Disclosure: The study was funded by Celgene and Acceleron Pharma. For full disclosures of the study authors, visit nejm.org.