Treatment of anemia in patients with lower-risk myelodysplastic syndromes using luspatercept

Abstract: Anemia is a leading clinical problem in patients with low-risk myelodysplastic syndromes (MDS). Until recently, its treatment was based on recombinant erythropoietin preparations, blood component transfusions, and iron chelation. The drug luspatercept is a fusion protein consisting of an activin receptor linked to the Fc domain of IgG, which binds the molecules from the TGF-beta superfamily present in circulation, including activin. This results in reduced activation of the TGF-beta signaling pathway, which is responsible for ineffective erythropoiesis in MDS patients, ultimately leading to an increase in hemoglobin levels. Since 2020, luspatercept has been approved by the FDA and EMA for the treatment of anemia in low-risk MDS patients with ring sideroblasts who are transfusion-dependent and have not responded to or are not candidates for erythropoietin based on the results from the MEDALIST trial. Subsequently, in 2024, it was approved as a first-line treatment for anemia in transfusion-dependent low-risk MDS patients, based on the results of the COMMANDS trial, which is analyzed in this article.

Key words:
anemia; erythropoietin; leukemia; luspatercept; myelodysplastic syndrome