Examining a Post-hoc Analysis from the COMMANDS Trial

A recent post‑hoc analysis of the COMMANDS trial evaluated the benefits of Luspatercept versus Epoetin alfa (EA) in ESA‑naïve, transfusion‑dependent patients with very low, low, or intermediate-risk Myelodysplastic Syndromes (LR‑MDS).

The trial found that luspatercept led to markedly higher rates of ≥12‑week red blood cell‑transfusion independence (RBC‑TI) and more durable responses compared with EA across disease severities. Benefit was particularly pronounced in patients with less advanced disease at baseline (e.g., Hb ≥ 8 g/dL, low transfusion burden, low serum EPO), but luspatercept still outperformed EA even in those with worse baseline markers. These results strengthen the rationale for using luspatercept as first-line therapy in LR‑MDS — especially earlier in the disease course — rather than reserving it as a second-line after ESA failure.