How the Frontline Indication for Luspatercept Impacts Anemia in MDS

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EP: 1.How the Frontline Indication for Luspatercept Impacts Anemia in MDS

EP: 2.Subgroup Analyses of COMMANDS Trial Favor Luspatercept in MDS

Amer Zeidan, MBBS, associate professor of internal medicine (Hematology), chief of hematologic malignancies and director of early therapeutics research for Hematology, and leader of the clinical research team for leukemias and myeloid malignancies at the Yale Cancer Center, discusses the data that led to the approval of luspatercept-amt (Reblozyl) to treat anemia in patients with myelodysplastic syndromes (MDS).

The initial approval for luspatercept was for certain adults with MDS who progressed on an erythropoiesis-stimulating agent (ESA) and needed 2 or more red blood cell (RBC) units over 8 weeks. These patients included those patients with very low- to intermediate-risk MDS with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis. This approval was based off the MEDALIST trial (NCT02631070), which met its primary end point of more patients being RBC-transfusion independent with luspatercept (37.9%) compared with those on placebo (24.6%).

Further research on the randomized phase 3 COMMANDS trial (NCT03682536) led to the expansion of the indication of luspatercept to the frontline setting for patients with anemia and lower-risk MDS. Zeidan discusses the rationale and design of the study, as well as how the use of luspatercept approximately doubled the proportion of patients who were RBC-transfusion independent compared with those patients on ESAs.

TRANSCRIPTION:

0:08 | Based on this, the COMMANDS trial was conducted, which tried to answer 2 questions. The first question was, what is the efficacy in the frontline setting against ESAs? And then the second question was about activity outside of the ring sideroblast setting. So, the COMMANDS study was a large international study, and actually, it was a positive study for the primary and many of the secondary end points. So, the main finding of COMMANDS was improvement in the rate of transfusion independence, which were for 12 weeks combined with a mean hemoglobin rise of 1.5 g/dL.

0:30 | This [occurred in] 60% with luspatercept compared to 30% with ESA, and based on this, the FDA has approved luspatercept also in the frontline setting for anemic patients who have anemia and who may require blood cell transfusions.