{"entity":{"id":"paper-commands-luspatercept-mds-lancet-2023","kind":"paper","name":"COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions","aka":[],"tldr":"In COMMANDS, luspatercept, a drug that frees late-stage red cell production from TGF-beta-family braking, freed 59% of transfusion-dependent MDS patients from transfusions for at least 12 weeks, against 31% with the standard erythropoietin injection.","summary":"COMMANDS randomised patients with lower-risk MDS (the three lowest risk categories) who were red-cell transfusion dependent and had not received erythropoiesis-stimulating agents to subcutaneous luspatercept every three weeks or weekly epoetin alfa. The primary endpoint was red-cell transfusion independence for at least 12 weeks with a concurrent haemoglobin rise of at least 1.5 g/dL within the first 24 weeks. In the interim analysis of 301 patients this was achieved by 58.5% versus 31.2%, with benefit in both ring-sideroblast-positive and negative disease, although the difference was smaller in patients without ring sideroblasts. Adverse events were similar, with fatigue, diarrhoea and hypertension more common with luspatercept.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=COMMANDS%20luspatercept%20epoetin%20alfa%20lower-risk%20MDS%20Platzbecker%20Lancet%202023"},{"label":"ClinicalTrials.gov NCT03682536","url":"https://clinicaltrials.gov/study/NCT03682536"}],"tags":[],"related":["paper-imerge-imetelstat-mds-lancet-2024"],"cancers":["mds"],"sections":[],"technologies":[],"targets":["tgf-beta"],"drugs":["luspatercept","imetelstat"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["orr"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-drug-pricing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)00874-7","pmid":"37311468","authors":"Platzbecker U, Della Porta MG, Santini V, et al.","paperType":"rct","findings":["Interim analysis of 301 ESA-naive, transfusion-dependent, lower-risk MDS patients; luspatercept vs epoetin alfa.","Primary endpoint (12-week transfusion independence plus haemoglobin rise of at least 1.5 g/dL in weeks 1-24): 58.5% vs 31.2%.","Benefit in ring-sideroblast-positive disease was largest; the effect in ring-sideroblast-negative disease was smaller and less certain.","Median duration of transfusion independence was longer with luspatercept.","Safety comparable; no increase in progression to AML."],"whatItMeans":"COMMANDS moved luspatercept from second line (after ESA failure, MEDALIST trial) to first line, offering transfusion-dependent lower-risk MDS patients a better chance of transfusion freedom from the start. It changed guidelines and labels in 2023. Erythropoietin remains a reasonable and cheaper option for patients without ring sideroblasts or with low transfusion burden.","caveats":["Interim analysis of an open-label trial; the composite primary endpoint is a surrogate for quality of life and survival.","Uncertain benefit in ring-sideroblast-negative and SF3B1-unmutated disease.","Excluded patients with del(5q) and those with high transfusion burden plus low erythropoietin only partially represented.","Cost is far higher than epoetin."],"changedPractice":true,"participants":301},"route":"/key-papers/paper-commands-luspatercept-mds-lancet-2023/","neighbours":{"paper":[{"id":"paper-imerge-imetelstat-mds-lancet-2024","kind":"paper","name":"IMerge: imetelstat, a telomerase inhibitor, for transfusion-dependent lower-risk MDS after erythropoietin has failed","route":"/key-papers/paper-imerge-imetelstat-mds-lancet-2024/"}],"cancer":[{"id":"mds-lower-risk","kind":"cancer","name":"Lower-risk myelodysplastic syndromes","route":"/cancers/mds-lower-risk/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"}],"pathway":[{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"}],"drug":[{"id":"imetelstat","kind":"drug","name":"Imetelstat","route":"/drugs/imetelstat/"},{"id":"luspatercept","kind":"drug","name":"Luspatercept","route":"/drugs/luspatercept/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"bottleneck":[{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}],"person":[{"id":"amer-zeidan","kind":"person","name":"Amer M. Zeidan","route":"/people/amer-zeidan/"},{"id":"uwe-platzbecker","kind":"person","name":"Uwe Platzbecker","route":"/people/uwe-platzbecker/"}]}}