FDA Approves Luspatercept-aamt for Anemia in Patients with Myelodysplastic Syndromes

On August 28, 2023, the U.S. Food and Drug Administration approved luspatercept-aamt (Reblozyl) for the treatment of anemia in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) without prior erythropoiesis-stimulating agent (ESA) use, as detected by the World Health Organization 2016 criteria and the Revised International Prognostic Scoring System classification.

Study ID number: NCT03682536

Approval was based on the COMMANDS trial, a phase 3 study that included 356 patients with MDS, confirmed using the criteria mentioned above. Patients were randomly assigned in 1:1 ratio to either receive Luspatercept or eptoin Alfa. Luspatercept-aamt was administered subcutaneously once every three weeks, starting at a dose of 1.0 mg/kg, which could be increased to 1.33 mg/kg and then to a maximum of 1.7 mg/kg. The median treatment duration was not specified in the article.

Efficacy was established on the primary endpoint of red blood cell transfusion independence (RBC-TI) for at least 12 weeks and a mean hemoglobin (Hb) increase of at least 1.5 g/dL within the first 24 weeks. 58.5% of patients receiving luspatercept-aamt achieved the primary endpoint, compared to 31.2% of those given epoetin alfa (P <.0001). Additionally, 67% of patients in the luspatercept arm achieved RBC-TI for at least 12 weeks during weeks 1 to 24, compared to 46% in the epoetin alfa arm (nominal P =.0002).

Common adverse effects included diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea, occurring in more than 10% of patients.

The study concluded that luspatercept-aamt showed superior efficacy in achieving RBC-TI and increasing Hb levels compared to epoetin alfa, representing an important advancement for patients with lower-risk MDS.