# COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions

Source: https://onco.cc/key-papers/paper-commands-luspatercept-mds-lancet-2023/  
OnCo record `paper-commands-luspatercept-mds-lancet-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: The Lancet
- Year: 2023
- DOI: 10.1016/S0140-6736(23)00874-7
- Authors: Platzbecker U, Della Porta MG, Santini V, et al.
- 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.
- What it means: 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.

## Sources

- PubMed search: https://pubmed.ncbi.nlm.nih.gov/?term=COMMANDS%20luspatercept%20epoetin%20alfa%20lower-risk%20MDS%20Platzbecker%20Lancet%202023
- ClinicalTrials.gov NCT03682536: https://clinicaltrials.gov/study/NCT03682536

## Connected records

- key papers: [IMerge: imetelstat, a telomerase inhibitor, for transfusion-dependent lower-risk MDS after erythropoietin has failed](https://onco.cc/key-papers/paper-imerge-imetelstat-mds-lancet-2024/)
- cancers: [Lower-risk myelodysplastic syndromes](https://onco.cc/cancers/mds-lower-risk/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/)
- pathways: [TGF-β signalling](https://onco.cc/pathways/tgf-beta/)
- drugs: [Imetelstat](https://onco.cc/drugs/imetelstat/), [Luspatercept](https://onco.cc/drugs/luspatercept/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/)
- terms: [Objective response rate (ORR)](https://onco.cc/terms/orr/)
- bottlenecks: [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)
- people: [Amer M. Zeidan](https://onco.cc/people/amer-zeidan/), [Uwe Platzbecker](https://onco.cc/people/uwe-platzbecker/)

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