Dr Garcia-Manero on the Impact of Luspatercept on Hematopoietic Lineages in Lower-Risk 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 clinical implications of treatment with luspatercept-aamt (Reblozyl) on erythroid, neutrophil, and platelet lineages, as well as its safety in transfusion-dependent, erythropoiesis-stimulating agent (ESA)–naive lower-risk, myelodysplastic syndrome (MDS).

Anemia is a primary concern in patients with lower-risk MDS, yet other cytopenias, such as neutropenia and thrombocytopenia, also play a critical role in treatment strategies and patient outcomes. Accordingly, investigators evaluated specific responses of cytopenias in 3 hematopoietic lineages: erythroid (HI-E), neutrophil (HI-N), and platelet (HI-P) in patients from the phase 3 COMMANDS trial (NCT03682536). Time to HI-E, prior and on-treatment transfusions, and safety were also assessed.

Results presented at the 2024 EHA Hybrid Congress showed that luspatercept significantly improved erythroid, neutrophil, and platelet lineages in the study population, Garcia-Manero states. Notably, a higher proportion of patients treated with luspatercept achieved HI-E compared to those treated with epoetin alfa, which is crucial given that erythroid improvement was the primary end point of the study, he reports.

However, the significance of these findings extends beyond erythroid response, Garcia-Manero continues. Although the sample size was limited for HI-P and HI-N assessments, and results were not statistically significant, more patients on luspatercept showed an improvement in platelet and neutrophil counts during the initial 24 weeks of treatment compared with epoetin alfa, he details. Luspatercept’s ability to improve platelet and neutrophil counts therefore suggests a broader hematopoietic benefit, Garcia-Manero says, adding that the lack of induced cytopenias also positions luspatercept as a safe treatment option.

Ultimately, the COMMANDS trial results underscore the potential of luspatercept to safely enhance hematopoietic function in multiple lineages in patients with lower-risk MDS, Garcia-Manero emphasizes. Future studies will hopefully elucidate the mechanisms behind these effects, as current data suggest that luspatercept may have roles beyond erythropoiesis, he concludes.