Myelodysplastic syndromes (MDS) are caused by a heterogeneous group of hematopoietic stem cell disorders and can progress to acute myeloid leukemia. Along with RBC transfusions, erythropoiesis-stimulating agents (ESAs), such as epoetin alfa, are the standard of care for patients with lower-risk MDS with anemia. Luspatercept, another ESA, has been approved after epoetin alfa treatment failure for these patients. To assess the safety and efficacy of luspatercept as a first line ESA in adults with lower-risk MDS requiring at least two RBC transfusions every 8 weeks, the phase 3 COMMANDS randomized controlled trial enrolled 356 ESA-naive adult patients in 26 countries with low- to intermediate-risk MDS requiring RBC transfusions to manage anemia. During the trial, 178 patients were randomized in each study arm to receive either luspatercept or epoetin alfa subcutaneously every three or one week, respectively, until either disease progression or 24 weeks without clinical benefit. Patients will be followed up to 5 years; however, an interim analysis of 147 patients in the luspatercept arm and 154 in the epoetin alfa arm who had completed either 24 weeks of treatment or discontinued treatment suggest that luspatercept lowered RBC transfusion dependence and increased hemoglobin levels. Specifically, 59% (86/147) of patients in the luspatercept arm reached transfusion independence for at least 12 weeks compared to 31% (48/154) of patients in the epoetin alfa arm (p<0.0001). Safety profiles were similar between the two ESAs, but further safety analyses are needed as well as confirming these results in other subgroups of patients with MDS.
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