Luspatercept approved for transfusion-dependent anemia in patients with MDS

Luspatercept-aamt is a first-in-class erythroid maturation agent. It reduces the inhibitory effect of the SMAD2-SMAD3 pathway on red cell maturation, which is reported to be increased in bone marrow cells of patients with myelodysplastic syndromes (MDS) with ineffective erythropoiesis.¹

The placebo-controlled phase III MEDALIST trial (NCT02631070) evaluated luspatercept in transfusion-dependent patients who do not respond to erythropoiesis-stimulating agents. A higher proportion of patients treated with luspatercept (38%) showed red blood cell transfusion independence for ≥ 8 weeks within the first 24 weeks compared with the placebo group (13%; p < 0.001). Additionally, a higher percentage of patients treated with luspatercept showed ≥ 12 weeks of independence in the first 24 weeks (28% vs 8% in luspatercept vs placebo group, respectively; p < 0.001) and 48 weeks (33% vs 12% in luspatercept vs placebo group, respectively; p < 0.001) of the trial compared with the placebo group.¹

Treatment-emergent adverse events of Grade 3 or 4 were reported in 42.5% of patients who received luspatercept vs 44.7% of patients who received placebo. The most common all-grade adverse events (occurring in ≥ 10% of patients) included fatigue, diarrhea, asthenia, nausea, dizziness, and back pain. Adverse events incidence reduced after the fourth cycle and was not associated with dose adjustment but led to treatment discontinuation in 8% of patients.¹

With the favorable results from the MEDALIST trial, the U.S. Food and Drug Administration (FDA) approved luspatercept on April 3, 2020, for the treatment of anemia failing an erythropoiesis-stimulating agent and requiring two or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts (MDS-RS), or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).²

Soon after the FDA approval, on June 25, 2020, the European Medicines Agency also approved luspatercept for its use in Europe for the treatment of adult patients with transfusion-dependent anemia due to very low, low, and intermediate-risk MDS-RS, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.³