On August 28, the U.S. Food and Drug Administration (FDA) approved luspatercept-aamt (Reblozyl) to treat anemia in adult patients with very low– to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell transfusions and who have not received previous erythropoiesis-stimulating agents.
This expanded indication to the first-line setting is based on interim results from the pivotal phase III COMMANDS trial (ClinicalTrials.gov identifier NCT03682536), in which luspatercept demonstrated superior efficacy of concurrent red blood cell transfusion independence and hemoglobin increase compared to epoetin alfa, an erythropoiesis-stimulating agent, regardless of ring sideroblast status. These results underscore luspatercept’s ability to address chronic anemia earlier in the treatment journey in a broader range of patients.
“For patients with lower-risk MDS, current standard therapies, including erythropoiesis-stimulating agents, have provided limited benefit in controlling anemia, with only one in three patients responding for a duration of 6 to 18 months,” said Guillermo Garcia-Manero, MD, lead investigator of the COMMANDS study and Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center. “Results from the COMMANDS study showed nearly twice as many patients treated with luspatercept achieved transfusion independence of at least 12 weeks and concurrent hemoglobin increase compared to epoetin alfa. [The FDA] approval represents an important advancement for patients with lower-risk MDS.”
COMMANDS Study Details
In the COMMANDS trial, results showed 58.5% (n = 86) of patients treated with luspatercept vs 31.2% (n = 48) of patients treated with epoetin alfa achieved the primary endpoint of red blood cell transfusion independence of at least 12 weeks, with a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks (P < .0001). The most common adverse reactions—reported in 10% or more of patients receiving lustpatercept—were diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.
Results from the COMMANDS study were featured in June as part of the press program at the 2023 ASCO Annual Meeting (Abstract 7003) and in a plenary session at the European Hematology Association 2023 Hybrid Congress (Abstract S102), with simultaneous publication by Platzbecker et al in The Lancet.
“The majority of patients with MDS experience chronic anemia and require red blood cell transfusions,” said Tracey Iraca, Executive Director of the MDS Foundation. “The approval of lustpatercept in the first-line treatment of anemia for patients with lower-risk MDS represents a crucial step in making transfusion independence possible for more patients.”
