Dr Garcia-Manero on the Efficacy of Luspatercept in Transfusion-Dependent MDS

Guillermo Garcia-Manero, MD, a professor, chief of the Section of Myelodysplastic Syndromes, deputy chair of Translational Research, and director of the Fellowship Program in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the key efficacy findings from the phase 3 COMMANDS trial (NCT03682536) evaluating luspatercept-aamt (Reblozyl) in patients with myelodysplastic syndrome (MDS) who were erythropoiesis-stimulating agent (ESA) naïve and red blood cell (RBC) transfusion dependent.

On August 28, 2023, the FDA approved luspatercept for the treatment of anemia without prior ESA use in adult patients with very low– to intermediate-risk MDS who may require regular RBC transfusions. The regulatory decision was based on data from COMMANDS.

Findings presented at the 2023 SOHO Annual Meeting showed that the study met its primary end point. Among patients treated in the luspatercept arm (n = 178), 58.5% remained RBC transfusion independent for 12 weeks or more with concurrent mean hemoglobin increase of at least 1.5 g/dL, compared with 31.2% of patients treated with the ESA epoetin alfa (n = 178; P < .0001). The median duration of RBC transfusion independence was 126.6 weeks with luspatercept vs 77.0 weeks with epoetin alfa (HR, 0.456; 95% CI, 0.260-0.798).

Anemia and transfusion dependency have represented significant problems for patients with MDS, and ESAs previously served as the only approved agents available to treat anemia in the frontline setting for this population, Garcia-Manero says. Although these agents provided a benefit, a need for improved therapies remained, he adds.

Luspatercept was previously approved by the FDA in April 2020 for the treatment of anemia failing an ESA and requiring 2 or more RBC units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. Those prior findings helped inform the design of the COMMANDS trial and ultimately helped pave the way for luspatercept as a new option in the frontline setting, Garcia-Manero concludes.