Darbepoetin alfa for treating anemia in patients with low-risk myelodysplastic syndromes: Exploratory analysis of baseline predictors of response

Abstract

6579 Background: Patients (pts) with myelodysplastic syndromes (MDS) often develop anemia, resulting in fatigue and increased transfusions. The erythropoiesis-stimulating agents (ESAs) epoetin alfa and darbepoetin alfa (DA) can raise hemoglobin (Hb) levels in low-risk MDS pts. Baseline (BL) endogenous erythropoietin (eEPO) levels, transfusion history, and FAB sub-type can be predictive factors of response to ESAs (Hellström-Lindberg et al., 2003). Methods: This is an ongoing, fully enrolled (n = 209), phase 2, single-arm, 52-week (wk) study of DA 500 mcg every three weeks (Q3W) for treating anemia (Hb ≤ 11 g/dL) in low- or intermediate-risk MDS pts. A planned interim analysis was done after 13 wks (n = 189). The primary endpoint is the proportion of pts with an erythroid response by 13 wks. Other endpoints include change in Hb levels and in FACT-F score from BL. Results are stratified by whether pts received an ESA before enrollment: ESA-naïve (ESA-N) pts vs ESA-treated (ESA-T) pts. Exploratory analyses of the percentage of pts with an erythroid response adjusted by BL eEPO or FAB category were done. Results: Of 130 ESA-N pts, 52% were women, 86% were white, 58% had refractory anemia (RA), 34% had RA with ringed sideroblasts (RARS), 8% had RA with excess blasts (RAEB), and the mean (SD) age was 74.8 (10.1) years. The 59 ESA-T pts had similar demographics. A majority of ESA-N pts had an erythroid response, achieved a target Hb of 11 g/dL, and had a clinically significant rise in FACT-F score; ESA-N pts with lower BL eEPO levels were more likely to have a major erythroid response ( Table ). A major erythroid response was seen in 50% of pts with RA (n = 111), in 30% of pts with RARS (n = 64), and in 23% of pts with RAEB (n = 13). Of all 189 pts, 78% had an adverse event (AE), 1 had a serious treatment-related AE (hypertension), and none had thrombotic events. Conclusions: These interim results suggest that FAB sub-type and BL eEPO may affect response. Final 13-wk data from all enrolled pts (n = 209) will be shown. [Table: see text] [Table: see text]