Luspatercept and ESA-based regimens show higher rates of erythroid haematological improvement in lower-risk MDSDifferent Medications Show Different Benefits for Myelodysplastic Syndromes

BackgroundThe comparative efficacy of pharmacological treatments for lower-risk myelodysplastic syndromes (LR-MDS) remains uncertain because head-to-head randomised evidence is limited.MethodsWe performed a systematic review and network meta-analysis of randomised controlled trials evaluating pharmacological treatments for LR-MDS. Outcomes of interest were haematological improvement–erythroid (HI–E), red blood cell transfusion independence (RBC–TI), haematological improvement–platelet (HI–P), and adverse events (AEs).ResultsWe included 20 trials (2,877 participants), of which 17 trials (2,670 participants) contributed to connected treatment networks. For HI–E, luspatercept and ESA-based regimens were associated with higher rates. Lenalidomide-containing regimens showed favourable RBC–TI outcomes, including lenalidomide plus ESA, lenalidomide with or without ESA and/or G-CSF, and lenalidomide monotherapy. For HI–P, eltrombopag and romiplostim showed potential benefits. Safety profiles differed across treatments: CC-486 and imetelstat were associated with higher odds of neutropenia and gastrointestinal toxicity, whereas luspatercept was associated with increased fatigue and AEs.ConclusionComparative treatment benefit in LR-MDS differs by clinical endpoint. These findings support an individualised, goal-directed treatment approach rather than a single universally superior therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251184384.