Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response
Por:
Villegas, A, Arrizabalaga, B, Fernandez-Lago, C, Castro, M, Mayans, JR, Gonzalez-Porras, JR, Duarte, RF, Remacha, AF, Luno, E, Gasquet, JA
Publicada:
1 may 2011
Resumen:
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.
Filiaciones:
Villegas, A:
Univ Complutense, Hosp Clin San Carlos, Dept Hematol, E-28040 Madrid, Spain
Arrizabalaga, B:
Hosp Cruces, Dept Hematol, Bilbao, Spain
Fernandez-Lago, C:
Hosp Juan Canalejo, Dept Hematol, Coruna, Spain
Castro, M:
Complejo Hosp Univ Vigo, Dept Hematol, Vigo, Spain
Mayans, JR:
Hosp Arnau Vilanova, Dept Hematol, Valencia, Spain
Gonzalez-Porras, JR:
Hosp Univ Salamanca, Dept Hematol, Salamanca, Spain
Duarte, RF:
Hosp Duran & Reynals, Dept Hematol, Ico Barcelona, Spain
Remacha, AF:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain
Luno, E:
Hosp Univ Cent Asturias, Dept Hematol, Oviedo, Spain
Gasquet, JA:
Amgen SA, Dept Med, Barcelona, Spain
Spanish Erythropathol Grp, Barcelona, Spain
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