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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.
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.
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.
Shares Uwe Platzbecker, Luspatercept, Lower-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS).
Shares Uwe Platzbecker, Imetelstat, Lower-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS).
Shares Luspatercept, Lower-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS), Bristol Myers Squibb.
Shares Imetelstat, Luspatercept, Lower-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS).
Shares Luspatercept, Myelodysplastic syndromes / neoplasms (MDS), Bristol Myers Squibb.
Shares Uwe Platzbecker, Myelodysplastic syndromes / neoplasms (MDS).
Shares Imetelstat, Luspatercept, Lower-risk myelodysplastic syndromes.
Shares Imetelstat, Luspatercept, Lower-risk myelodysplastic syndromes.