Real-World Luspatercept Evidence in Myelodysplastic Neoplasms: A Systematic Review and Bayesian Meta-Analysis

Luspatercept has emerged as a therapeutic option for patients with lower-risk myelodysplastic neoplasms (MDS). Nonetheless, the performance of luspatercept outside of controlled clinical trials remains unclear. We aimed to synthesize real-world evidence (RWE) on the effectiveness and safety of luspatercept. This study was conducted following PRISMA guidelines. We searched for studies up to June 2025 evaluating luspatercept in adult MDS patients. Data on hematologic improvement-erythroid (HI-E), transfusion independence (TI at 8, 12, and 16 weeks), adverse events, and overall survival (OS) were extracted. Bayesian random-effects meta-analyses were performed using priors derived from pooled clinical trials. Seventeen studies were included: five clinical trials (440 patients) and twelve real-world cohorts (1821 patients). The pooled estimate for HI-E was 46.6% (95% CrI: 32.5%-63.9%). For TI, pooled rates at 8, 12, and 16 weeks were 44.7% (95% CrI: 28.6%-61.5%), 38.6% (95% CrI: 21.1%-60.0%), and 30.9% (95% CrI: 10.7%-53.9%), respectively. The subgroups with highest TI and HI-E were patients with positive SF3B1 status (58.5%, at 8 weeks) and Asian patients (54.8%), respectively. Male sex was associated with lower HI-E, 8, and 12 weeks TI rates. Hypertension and falls were more frequently reported in RWE. We estimated OS rates of 88.9% at 1 year and 74.4% at 2 years following treatment initiation. Real-world HI-E were modestly attenuated, likely reflecting selection, adherence, and monitoring differences. The response seems dependent on disease, geographical, and demographical moderators. Such aspects should be taken into account in the design of future studies and in clinical decisions.