Dr Ball on the Use of Luspatercept in MDS With Anemia

Somedeb Ball, MBBS, assistant professor, medicine, Division of Hematology Oncology, Department of Medicine, Vanderbilt University Medical Center, discusses the benefits of luspatercept-aamt (Reblozyl) for patients with anemia due to their myelodysplastic syndrome (MDS).

Luspatercept is a fusion protein that contains a modified activin receptor that acts on the TGF-β ligand and improves upon outcomes with late erythropoietin-stimulating agents (ESAs) to alleviate anemia in patients with MDS, Ball says. Early research has shown that luspatercept is active in patients with MDS with anemia that is refractory to prior ESAs, Ball notes. In 2020, the FDA approved luspatercept for adult patients with lower-risk MDS with anemia with ring sideroblasts who have progressed on an ESA and require at least 2 red blood cell (RBC) units across 8 weeks. Data from the pivotal phase 3 MEDALIST trial (NCT02631070), which supported the approval, also showed that this agent was effective in patients with SF3B1 mutations.

Luspatercept was further evaluated in ESA-naive patients with anemia due to lower-risk MDS requiring RBC transfusions in the randomized, phase 3 COMMANDS trial (NCT03682536), findings from which were presented at the 2023 ASCO Annual Meeting and 2023 EHA Congress. In the phase 3 trial, luspatercept was compared with epoetin alfa, the previous frontline standard of care for patients with lower-risk MDS with transfusion-dependent anemia, according to Ball. The primary end point of COMMANDS was RBC transfusion independence for at least 12 weeks with a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks.

In COMMANDS, 58.5% of patients in the luspatercept arm achieved the primary end point compared with 31.2% of those in the epoetin alfa arm. The benefit with luspatercept was consistent across patient subgroups when patients were stratified by baseline serum erythropoietin levels, baseline RBC transfusion burden, SF3B1 mutation status, and ring sideroblast status, Ball emphasizes. Data from COMMANDS supported the 2023 FDA approval of luspatercept for the treatment of anemia in ESA-naive patients with very low– to intermediate-risk MDS who may require regular RBC transfusions.