Real-World Outcomes From 1L ESA vs Luspatercept Use in LR-MDS

Real-World Outcomes from 1L ESA vs Luspatercept Use in LR-MDS

Experts present real-world data comparing frontline ESAs vs luspatercept in lower-risk MDS. Unlike those from controlled clinical trial populations, these analyses captured outcomes from routine practice, reflecting older, more comorbid patients with variable adherence. A retrospective chart review spanning late 2024 through early 2025 included over 200 patients, divided between ESA- and luspatercept-treated groups. The primary end point—transfusion independence for 12 weeks or more plus a hemoglobin increase of 1.25 g/dL or greater—showed nearly double the response rate with luspatercept compared with ESAs, consistent with COMMANDS trial findings.

Subgroup analyses confirmed that patients with SF3B1 mutations, particularly those with concomitant TET2 or DNMT3A variants, derived the strongest benefit from luspatercept, with transfusion independence rates approaching 50%. Importantly, patients who were SF3B1-negative but had baseline erythropoietin levels below 200 IU/L also responded meaningfully, though to a lesser degree. These data reinforce the concept that both molecular status and serum EPO level are predictive biomarkers for frontline therapy selection. Clinicians highlight that the real-world findings support luspatercept as a preferred 1L choice in SF3B1-positive patients, while also offering substantial efficacy in select SF3B1-negative subgroups.

Panelists debate optimal end points in this setting, noting that 12-week transfusion independence plus hemoglobin gain is both practical and patient relevant. However, they emphasize the importance of incorporating longer-term outcomes such as durability, cardiovascular safety, and quality-of-life measures. Clinicians express interest in moving beyond rigid hemoglobin thresholds—traditionally capped at 12 g/dL due to ESA safety concerns—to more individualized targets that better reflect functional improvement. Overall, the real-world evidence strengthens the case for luspatercept as a frontline standard in LR-MDS, while also underscoring the need to refine efficacy end points and integrate patient-reported outcomes in future studies.