Early ESA Use Improves Hematologic Response Duration in Patients With Lower-Risk MDS, Anemia

The phase 3 EPO-PRETAR trial showed that starting erythropoiesis-stimulating agents (ESAs) early in participants with lower-risk myelodysplastic syndrome (MDS) and anemia significantly improved hematologic erythroid response and duration. However, the timing of ESA initiation did not affect progression to red blood cell (RBC) transfusion dependence or survival outcomes.

Lower-risk MDS is characterized by ineffective RBC production, which often leads to anemia that requires intervention. Although ESAs are the standard first-line treatment for anemia, the optimal timing for their initiation remains unclear. In a retrospective study, treatment with an ESA within six months of diagnosis delayed the time to RBC transfusion dependence in lower-risk MDS participants.¹ To confirm these results prospectively, the open-label, randomized, multicenter phase 3 EPO-PRETAR trial (NCT03223961) compared early versus delayed ESA use in lower-risk participants with MDS and anemia without RBC transfusion dependence. Sophie Park, MD, Centre Hospitalier Universitaire de Grenoble Alpes, France, presented the results.²

In the multicenter study, 84 participants received weekly epoetin alfa (60,000 IU) either immediately (early initiation at hemoglobin levels of 9–10.5 g/dL) or in a delayed fashion once hemoglobin levels warranted transfusion (late initiation, hemoglobin levels 8–9 g/dL). All participants had baseline hemoglobin levels of 9 to10.5 g/dL, were treated for at least 12 weeks, and were followed up for a median of 34 months.

Early ESA initiation resulted in a significantly greater hematologic improvement–erythroid (HI-E) of 79.5%, compared with 54.2% in the delayed group. Early initiation also prolonged HI-E response duration, with the median hematologic improvement lasting 30.6 months versus 12.7 months in the delayed treatment group. Despite these hematologic benefits, the median time to RBC transfusion dependence was similar between the two groups at 36.4 months. No differences between early and late ESA initiation were observed regarding progression-free survival, overall survival, or quality of life. Transformation to higher-risk MDS or acute myeloid leukemia also occurred at similar rates.

HI-E and time to RBC transfusion dependence correlated with lower serum erythropoietin levels and lower Molecular International Prognostic Scoring System (IPSS-M) scores in participants receiving ESA. Gene expression analysis differentiated ESA responders from nonresponders regarding adaptive and innate immunity pathway genes and identified erythropoiesis markers associated with progression to transfusion dependence.

Park concluded, “Early introduction of ESA in lower-risk MDS participants with anemia increased erythroid response and duration, but did not delay the time to RBC transfusion dependence from inclusion, and did not impact progression-free and overall survival and quality of life.”

REFERENCES

1 Park S, Kelaidi C, Sapena R, et al. Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. Leuk Res. 2010;34(11):1430-1436. doi: 10.1016/j.leukres.2010.05.030

2 Park S, Slama B, Moldovan M, et al. Early versus late onset of ESA in lower risk anemic MDS patients: results of the GFM randomized phase III EPO-Pretar. Abstract #349.  Presented at the ASH Annual Meeting; December 7-10, 2024; San Diego, California