Lower-Risk MDS Treatment Paradigms and Considerations for Transfusion and Pharmacologic Therapies

Video content above is prompted by the following:

The treatment landscape for lower-risk myelodysplastic syndrome (MDS) has evolved significantly, offering patients multiple therapeutic options beyond the traditional erythropoiesis-stimulating agents (ESAs) that were never formally FDA-approved but served as the de facto standard of care. Current National Comprehensive Cancer Network guidelines reflect these advances, providing specific recommendations based on patient characteristics: lenalidomide for patients with deletion 5q, luspatercept as a category 1 preferred option for ring sideroblast–positive patients, and imetelstat for patients with baseline erythropoietin (EPO) levels greater than 500.

The decision-making process for initiating treatment has become more nuanced, with clinicians considering both clinical and nonclinical factors. Key triggers for shifting from watch-and-wait to pharmacological therapy include symptomatic anemia and impending transfusion requirements. The FDA approval of imetelstat in June 2024, based on the global IMERGE trial, has expanded options particularly for heavily transfused patients who progressed after ESA therapy or those with high baseline EPO levels exceeding 500.

For ring sideroblast–negative patients, treatment options include ESAs (for baseline EPO <500) and luspatercept, with the choice individualized based on patient factors and treatment goals. This personalized approach recognizes that patients with worse anemia and higher transfusion burden are less likely to respond to available therapies, emphasizing the importance of early intervention when clinically appropriate. The expanded therapeutic arsenal has transformed lower-risk MDS management from a limited to a comprehensive treatment paradigm.