Debate: Inflection Point for LR-MDS Therapy: Serum EPO >200 U/L vs Serum EPO >500 U/L

EP: 1.Early vs Late Onset of ESA in LR-MDS: Results From Phase 3 EPO-PRETAR Trial

EP: 2.COMMANDS and ELEMENT-MDS Trials: Long-Term Analysis, Survival, Duration of Response, and Hemoglobin Levels

EP: 3.IMerge Trial

EP: 4.Debate: Optimal Initiation of ESAs, Luspatercept, and Imetelstat: Pretransfusion vs Posttransfusion

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EP: 5.Debate: Inflection Point for LR-MDS Therapy: Serum EPO >200 U/L vs Serum EPO >500 U/L

EP: 6.Debate: Sequencing Therapies for LR-MDS: ESA First vs Luspatercept First

The discussion centered on treatment strategies for lower-risk myelodysplastic syndromes (MDS) based on serum erythropoietin (EPO) levels. It was noted that patients with serum EPO levels above 200 generally show lower and less durable responses to erythropoiesis-stimulating agents (ESAs). Historically, responses to ESAs have been observed up to EPO levels near 500, but effectiveness diminishes significantly beyond 200. Given the availability of newer therapies, there is a growing preference for initiating these agents over ESAs in patients with higher EPO levels, although some clinicians still consider ESAs in select cases due to their favorable safety profile.

While ESAs are less effective at higher EPO levels, their adverse effect profile remains an important consideration. Newer agents may cause fatigue and cytopenias such as thrombocytopenia and neutropenia, which can limit their tolerability. Data also support the use of these agents in patients who are refractory to ESAs, but evidence is limited on starting treatment with ESAs before transitioning to newer drugs. The 5-year survival data and evolving treatment landscape highlight the importance of personalized treatment sequencing, especially for patients with specific genetic mutations and ring sideroblast features that influence therapeutic responses.

For patients with serum EPO levels exceeding 500, treatment decisions are more complex. Some favor newer agents for their efficacy in certain mutational subtypes, while others weigh practical aspects such as administration logistics and patient convenience. Infusion requirements, frequency, and clinic resource management also impact therapy choice, with considerations for both patient burden and healthcare system efficiency. Overall, treatment selection should balance efficacy, adverse effect profiles, patient-specific factors, and logistical feasibility, as ongoing research continues to refine optimal approaches for this diverse patient population.