Early Epoetin Alfa Improves Erythroid Response Without Delaying Transfusion Dependence in Lower-Risk Myelodysplastic Syndromes
Clinical Summary:
- Design/Population: This open-label, phase 3 trial compared early and delayed epoetin alfa initiation in patients with non–transfusion-dependent lower-risk myelodysplastic syndromes and anemia.
- Key Outcomes: Early epoetin alfa significantly increased erythroid response rates but did not delay progression to red blood cell transfusion dependence or improve overall or progression-free survival compared with delayed initiation. Treatment was well tolerated, with no unexpected safety signals or differences in quality of life.
- Clinical Relevance: These findings suggest that timing of epoetin alfa should be individualized according to patient symptoms and preferences rather than initiated routinely before transfusion dependence develops.
Results from the phase 3 EPO-PRETAR trial demonstrated that early initiation of epoetin alfa did not delay progression to transfusion dependence in patients with lower-risk myelodysplastic syndromes (MDS), although it significantly improved early erythroid response rates and produced durable hematologic benefit.
These results were presented by Sophie Park, MD, PhD, Centre Hospitalier Universitaire de Grenoble, Grenoble, France, at the European Hematology Association (EHA) Congress in Stockholm, Sweden.
In this multicenter, open-label trial, 84 patients with lower-risk, non-transfusion-dependent MDS and anemia were randomized to receive epoetin alfa initiated at either trial enrollment (n = 43) or at the institution-defined hemoglobin threshold for red blood cell transfusion (n = 41). The primary end point was time to red blood cell transfusion dependence. Key secondary end points included erythroid response, duration of response, overall survival (OS), progression-free survival (PFS), acute myeloid leukemia (AML) transformation, safety, and quality of life.
After a median time to epoetin alfa initiation of 0.2 months in the early treatment arm and 16.2 months in the delayed treatment arm, no significant difference in time to transfusion dependence was observed (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.48 to 1.68; P = .74). Red blood cell transfusion dependence developed in 49% of patients in the early treatment arm and 46% patients in the delayed treatment arm.
Despite the lack of benefit for the primary end point, early treatment significantly improved hematologic response. At 12 weeks after epoetin alfa initiation, erythroid response was achieved in 85% of patients in the early treatment arm and 55% in the delayed treatment arm (risk ratio, 1.57; 95% CI, 1.12 to 2.2; P = .003). Median duration of erythroid response also numerically favored early treatment (32.7 months vs 24.9 months), although this difference was not statistically significant (P = .18).
OS and PFS were similar between treatment groups. Median PFS was 51 months in the early treatment arm and 38 months in the delayed treatment arm (HR, 0.91; 95% CI, 0.51 to 1.63; P = 0.75), while OS did not differ significantly (HR, 0.84; 95% CI, 0.44 to 1.61; P = .60). AML transformation occurred in four patients in each treatment arm.
Epoetin alfa was well tolerated, with no unexpected safety signals observed. Quality-of-life trajectories were also similar between the two treatment strategies.
“These findings support tailoring the timing of [erythropoiesis-stimulating agent] initiation to patient symptom burden and preferences, balancing the high probability of early hematologic improvement with the absence of demonstrated impact on transfusion dependence or survival,” concluded Dr Park.
Source:
Park S, Slama B, Moldovan M, et al. Early versus delayed ESA in lower-risk non-transfusion-dependent MDS: Final phase III EPO-PRETAR results on transfusion dependence and erythroid response. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-4111.
