On April 3, the U.S. Food and Drug Administration (FDA) approved luspatercept-aamt (Reblozyl) for the treatment of anemia that fails to respond to an erythropoiesis-stimulating agent and requires two or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Efficacy was demonstrated in MEDALIST, a randomized, multicenter, double-blind, placebo-controlled trial in 229 patients with International Prognostic Scoring System (IPSS-R) very low–, low-, or intermediate-risk myelodysplastic syndromes who had ring sideroblasts and required red blood cell transfusions (two or more red blood cell units over 8 weeks). Patients were randomly assigned 2:1 to luspatercept-aamt or placebo. All patients received best supportive care, which included red blood cell transfusions.
The main efficacy endpoint in MDS-RS and MDS-RS-T was the proportion of patients who were red blood cell transfusion–independent, defined as the absence of any transfusion during any consecutive 8-week period between weeks 1 and 24.
Of the 153 patients who received luspatercept-aamt, 58 (37.9%, 95% confidence interval [CI] = 30.2–46.1) were red blood cell transfusion–independent for at least 8 weeks, compared to 10 patients (13.2%, 95% CI = 6.5–22.9) who received placebo (treatment difference = 24.6% [95% CI = 14.5–34.6, P < .0001]).
The most common (> 10%) adverse reactions to luspatercept-aamt were fatigue, headache, musculoskeletal pain, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, and hypersensitivity.
The recommended starting dose of luspatercept-aamt is 1 mg/kg once every 3 weeks by subcutaneous injection, with a review of hemoglobin results prior to each administration.