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

Guillermo Garcia-Manero, MD, professor, chief, Section of Myelodysplastic Syndromes, chair, Translational Research, fellowship program director, Department of Leukemia, Division of Cancer Medicine, chair, faculty senate, The University of Texas MD Anderson Cancer Center, discusses the investigation of luspatercept-aamt (Reblozyl) vs epoetin alfa in patients with erythropoiesis-stimulating agent (ESA)–naïve, lower-risk myelodysplastic syndromes (MDS) and disease-related anemia who requires red blood cell (RBC) transfusions.

At the 2023 SOHO Annual Meeting, the phase 3 COMMANDS trial (NCT03682536) was reported to have met its composite primary end point of RBC transfusion independence (RBC-TI). Of the 178 patients in the luspatercept arm and the 178 patients in the ESA epoetin alfa arm, 58.5% vs 31.2%, respectively, remained RBC-TI for 12 weeks or more with a concurrent mean hemoglobin increase of at least 1.5 g/dL (P < .0001).

Notably, the FDA approved luspatercept in August, 2023, for the treatment of anemia in patients who have notreceived prior ESA treatment, have very low– to intermediate-risk MDS , and may require regular RBC transfusion. This regulatory decision was based on data from the multicenter, global COMMANDS trial.

In a presentation of the data, Garcia-Manero shared that 73% of patients in the luspatercept arm and 71.9% of patients in the ESA epoetin alfa arm had ring sideroblastics. Moreover, this analysis was conducted in the intent-to-treat population, Garcia-Manero emphasizes. However, questions remain regarding the activity of this compound in other patient subsets, he explains.

Moreover, Garcia-Manero notes that the duration of response with luspatercept was is longer in the ring sideroblastic subset. Based on these data, most patients with this disease will be treated with luspatercept going forward, Garcia-Manero concludes.