An exploratory analysis of transfusion risk when initiating darbepoetin alfa (DA) therapy at baseline hemoglobin (Hb) < 9 g/dl vs 9 to < 10 g/dl versus ≥ 10 g/dl in patients (pts) with chemotherapy-induced anemia (CIA).

Abstract

9077 Background: DA is an erythropoiesis-stimulating agent (ESA) approved in the US and EU to treat CIA based on controlled studies showing a reduction in transfusion needs and an increase in Hb levels. Due to recent ESA safety concerns, a Hb level of 10 g/dL for ESA initiation was recently instituted for CIA pts. Here we show an exploratory analysis of phase III trial data stratified by the baseline Hb (< 9 g/dL vs 9 to < 10 g/dL vs ≥ 10 g/dL) at DA initiation in CIA pts. Methods: Pts with CIA (Hb < 11 g/dL), nonmyeloid malignancies, and ECOG performance status ≤ 2 were randomized to DA 500 mcg Q3W or DA 2.25 mcg/kg QW for 15 weeks. Pts with Hb ≤ 8 g/dL or anemia symptoms could receive transfusions. A prior trial report showed DA 500 mcg Q3W was non-inferior to 2.25 mcg/kg QW for reducing transfusions from week 5 to end-of-the-treatment period (EOTP) (the primary endpoint). The current exploratory analysis examined transfusion, Hb, and safety outcomes by baseline Hb at DA initiation. Results: Of 705 randomized pts, baseline Hb was < 9 g/dL in 126 pts (18%), 9 to < 10 g/dL in 225 pts (32%), and ≥ 10 g/dL in 354 pts (50%). With each lower Hb stratum of DA initiation, transfusion rates progressively increased while the percentage of pts with a 1 g/dL Hb rise in 14 days (with no transfusions) progressively decreased (Table). Incidence of deaths was highest in the < 9 g/dL Hb group while incidence of venous thromboembolic events (VTEs) was highest in the ≥ 10 g/dL Hb group. Conclusions: Transfusion rates with DA use progressively increased with lower Hb levels at DA initiation. Starting DA close to 10 g/dL Hb may reduce transfusion risk when following recommendations to initiate ESAs at a Hb level ≤ 10 g/dL. Baseline Hb at DA initiation < 9 g/dL (N = 126) 9 to < 10 g/dL (N = 225) ≥ 10 g/dL (N = 354) K-M % transfusions, week 1 to EOTP (95% CL) 62 (54,71) 35 (29,42) 19 (15,24) K-M % transfusions, week 5 to EOTP (95% CL) [N] 55 (46, 65) [119] 30 (24, 37) [212] 17 (13, 21) [341] 1 g/dL Hb rise in 14 days, n (%) 59 (47) 143 (64) 252 (71) Serious adverse events, n (%) 64 (51) 94 (42) 115 (32) VTEs, n (%) 7 (5.6) 10 (4.4) 24 (6.8) Deaths on study, n (%) 24 (19) 32 (14) 34 (10) Abbreviation: K-M, Kaplan-Meier. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Amgen Europe GmBH Amgen Amgen Amgen, Hospira, Ortho Biotech, Sandoz Amgen Amgen