Darbepoetin Alfa for the Treatment of Anemia in Patients with Myelodysplastic Syndrome.

Background: Anemia is one of the main problems associated with myelodysplastic syndrome (MDS) leading to fatigue, increased red blood cell transfusions, and reduced quality of life. Erythropoiesis-stimulating proteins (ESPs) have been used to treat MDS-induced anemia. Darbepoetin alfa (Aranesp^®) is a unique ESP that can be administered less frequently than recombinant human erythropoietin (rHuEPO) due to its longer serum half-life, increasing patient convenience and possibly enhancing treatment compliance.

Methods: We performed a retrospective analysis of medical records from anemic patients with confirmed MDS that had been treated with darbepoetin alfa in 2004 in 9 Spanish centers. Data were collected 16 weeks before and 16 weeks after the starting date of darbepoetin alfa treatment. Response to darbepoetin alfa was evaluated using the International Working Group criteria.

Results: This study included data from 81 patients. Median age was 70 years (range, 38.0 – 87.0) at diagnosis and 75 years (range, 39.0 – 91.0) at the beginning of treatment with darbepoetin alfa. The proportion of female patients was 56.8%. French-American-British (FAB) classification: 39.5% refractory anemia (RA), 46.9% RA with ringed sideroblasts (RARS), 9.9% RA with excess blasts (RAEB), 1.2% RAEB in transformation (RAEB-T), and 2.5% chronic myelomonocytic leukemia (CMML). International Prognostic Scoring System (IPSS) classification: 55.3% low; 36.2% intermediate-1 and 8.5% intermediate-2. ECOG status: 0–1 in 79% of patients. Median baseline hemoglobin level was 8.9 g/dL (range, 8.4 – 9.1). Previous treatment with recombinant human erythropoietin (rHuEPO) occurred in 44.4% of patients and time from last rHuEPO dose to initiation of darbepoetin alfa treatment was lower than 1 week in 53.1% of patients (average of 16.7 weeks; range, 0.0–159.0). Starting darbepoetin alfa dose was 150 mcg/week in 69.1% and 300 mcg/week in 29.6% of patients. Darbepoetin alfa dose was increased in 18.5% and reduced in 9.9% of patients. Median time until dose adjustment was 8 weeks. Granulocyte colony-stimulating factor (G-CSF, Filgrastim) support was required in 6.5% of patients and this percentage was maintained during the 16-week followup. A total of 69 patients (34 rHuEPO-naïve and 35 rHuEPO-treated) were evaluable for efficacy analysis (Hb and transfusion data available). Erythroid response was achieved in 55% of patients (29% major and 26% minor) with 65% of rHuEPO-naïve responders and 46% of rHuEPO-treated responders. A total of 66% responses were achieved before or at week 8.

Conclusion: These results indicate that darbepoetin alfa treatment appears to be effective in patients with MDS regardless of whether or not they had received previous treatment with rHuEPO.