Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response

Current guidelines support the use of erythropoiesis-stimulating agents for the treatment of anemia associated with low-risk myelodysplastic syndromes (MDS). Single-arm, open-label, multi-center, phase 2 trial that evaluated the efficacy and safety of darbepoetin alfa (DA) in patients with low or intermediate-risk MDS, hemoglobin < 100 g/L, erythropoietin (EPO) levels < 500 IU/L and transfusion requirements < 2 units/month over the preceding 2 months. Erythroid response (major [MaR] or minor [MiR]) and fatigue (Functional Assessment of Cancer Therapy--Fatigue [FACT-F]) were evaluated at 8, 16 and 24 weeks. DA was initiated at 300 mu mu g weekly. For patients who did not achieve MaR by 8 weeks, filgrastim 300 mu mu g weekly was added. clinicaltrials.gov identifier: NCT01039350. Forty-four patients (72.7%% transfusion independent) were included. Median age was 76.0 years (range 41.3--92.4), 54.5%% were male, and 90.9%% presented ECOG Status (0--1). Eighteen patients received filgrastim. An erythroid response was achieved by 31 of 44 patients (70.5%%) at week 8 (47.7%% MaR, 22.7%% MiR), 31 of 44 patients (70.5%%) at week 16 (61.4%% MaR, 9.1%% MiR), and 32 of 44 patients (72.7%%) at week 24 (61.3%% MaR, 11.4%% MiR). Mean (95%% CI) change in FACT-F at week 24 was 3.61 (0.72 to 6.51). Baseline EPO levels < 100 IU/L were a predictive factor of response. DA was well tolerated. Four mild (two iron deficiencies, flu syndrome and headache) and one fatal (thromboembolic event) adverse events were considered related to darbepoetin alfa. A fixed dose of 300 mu mu g of darbepoetin alfa weekly (with or without filgrastim) seems to be an effective and safe treatment for anemic patients with low or intermediate-risk MDS, low transfusion burden and EPO levels < 500 IU/L. Results may not be extrapolable to unselected MDS patients.