Impact of Mutational Landscape and Burden on RBC Transfusion Response in Patients With Lower-Risk Myelodysplastic Syndromes (LR-MDS) in the COMMANDS Study

The COMMANDS trial established luspatercept as a first-line treatment for anemia anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. in transfusion-dependent lower-risk (LR) myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (MDS). Here we report red blood cell red blood cell: The most numerous type of blood cell in healthy people. Red blood cells contain hemoglobin, a protein that picks up oxygen in the lungs and brings it to cells in all parts of the body. Also called erythrocyte, RBC. (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa epoetin alfa: Epoetin alfa can help improve red blood cell counts in bone marrow failure disease patients whose natural erythropoietin levels are low. It is given by injection under the skin (subcutaneous) or in the vein (intravenous). Epoetin alfa is approved by the U.S. Food and Drug Administration (FDA) for… in the COMMANDS trial. Of 350 evaluable patients, 238 (68.0%) had MDS with multiple lineage dysplasia and ring sideroblasts (RS) according to World Health Organization 2016 criteria, and 320 (91.4%) had somatic mutations in ≥ 1 gene (median, 2) with median variant allele frequencies (VAF) of 2%-59%. Mutation Mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. profiles were similar in the treatment groups. Luspatercept had superior responses versus epoetin alfa across multiple mutations (risk difference; RD, [95% confidence interval; CI] 0.25 [0.15-0.35]), including in SF3B1-mutated (0.38 [0.25-0.50]) and SF3B1 wild-type (0.09 [-0.11 to 0.30]). Luspatercept demonstrated superior responses in patients with VAF ≥ 10% (random effect, 0.36 [95% CI, 0.28-0.44]), and in those with 1 (63% vs. 40%; p = 0.040), 2 (70% vs. 27%; p < 0.001), and 3 (72% vs. 40%; p = 0.018) mutations, and across the low (75% vs. 38%), moderate low (61% vs. 38%), moderate high (44% vs. 21%), and high (36% vs. 24%) Molecular International Prognostic Scoring System International Prognostic Scoring System: A system that turns patient data into a score. The score tells how quickly a myelodysplastic syndrome (MDS) case is progressing and helps predict what may happen with the patient's MDS in the future. Also called IPSS. risk groups (summary effect RD, 0.26 [95% CI, 0.14-0.37]). Across most mutations luspatercept responses were superior (random effect, 0.34 [95% CI, 0.24-0.44]) in patients with RS but were similar between treatments in RS-negative patients. Luspatercept represents an effective treatment option in various mutational backgrounds in LR MDS. Trial Registration: ClinicalTrials.gov Identifier: NCT03682536.