Perspectives of Early vs Late Initiation of ESAs for Patients With Lower-Risk MDS

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The optimal timing for erythropoiesis-stimulating agent (ESA) initiation in lower-risk myelodysplastic syndrome (MDS) has been addressed by the phase 3 EPO-PRETAR trial presented at American Society of Hematology 2024, which randomly assigned 84 patients with baseline hemoglobin between 9 and 10.5 g/dL into early vs late initiation groups. The early group started ESA therapy immediately, while the late group initiated treatment when hemoglobin dropped below 9 g/dL. The primary end point was time to transfusion dependence, with secondary end points including progression-free survival, overall survival, health-related quality of life, and hematologic improvement duration.

Results demonstrated no significant difference in time to transfusion dependence between groups, nor in progression-free survival, overall survival, or health-related quality of life measures. However, the early initiation group showed significantly greater hematologic improvement and longer duration of hematologic improvement based on validated International Working Group 2018 criteria. These findings suggest short-term hemoglobin benefits with early ESA initiation but no demonstrated long-term advantages in disease progression or survival outcomes.

The study’s limitations include a relatively short median follow-up of 34 months, which may be insufficient to assess long-term measures adequately. The takeaway emphasizes that ESA initiation timing remains an individualized clinical decision, with early initiation providing hemoglobin improvements that may benefit symptomatic patients but without proven impact on survival or disease progression. These data support flexible, patient-centered approaches to ESA timing rather than rigid treatment algorithms, allowing clinicians to tailor therapy based on individual patient symptoms and circumstances.