Anemia is a major morbidity associated with low- and intermediate-risk myelodysplastic syndrome (MDS), and patients with MDS often become dependent on red blood cell (RBC) transfusion to counteract symptoms of anemia. Luspatercept, a first-in-class erythroid-maturation agent, is involved in regulation of late stage RBC maturation and is currently being investigated as a treatment for patients experiencing MDS-related anemia. At the plenary session of the American Society for Hematology (ASH) Annual Meeting, Alan List, MD (Moffitt Cancer Center, Tampa, Florida, United States), presented results from the randomized, double-blind, placebo-controlled, phase III Medalist trial (N = 229), which evaluated the impact of luspatercept (1 mg/kg subcutaneously every 21 days) on anemia associated with low- to intermediate-risk MDS.
Patients with very low- , low-, or intermediate-risk MDS were eligible to participate in the study if they had ≥15% ring sideroblasts in the bone marrow or if they had ≥5% ring sideroblasts with SF3B1 gene mutation and had <5% bone marrow blasts, were RBC transfusion dependent for at least 16 weeks, and who were refractory/unresponsive or ineligible for treatment with erythropoietin stimulating agents (ESA).
The study met its primary endpoint, with 37.9% of patients receiving luspatercept achieving RBC transfusion independence (RBC-TI) for ≥8 weeks, versus only 13.2% of patients receiving placebo (OR 5.1, P<.0001). A significantly greater proportion of patients in the luspatercept arm achieved RBC-TI for ≥12 weeks (28.1 vs 7.9; P = .0002) and had higher rates of erythroid hematologic improvement (HI-E) compared with the placebo (52.9% vs 11.8%; P<.0001).
The luspatercept was very well tolerated with a safety profile consistent with that seen in the phase II PACE-MDS study. Fatigue and muscle pain were the most common adverse events (AEs).
Dr List concluded that that luspatercept is a potential new treatment option for patients with lower-risk MDS-related anemia. Luspatercept is also being investigated in patients with low- to intermediate-risk MDS who have not previously received an ESA in the phase III COMMANDS study.