Idarubicin and cytarabine with clofarabine or fludarabine in adults with newly diagnosed acute myeloid leukemia: Updated results of a randomized phase II study.

Abstract

7037 Background: The purine nucleoside analogues fludarabine and clofarabine are effective agents in the treatment of acute myeloid leukemia (AML). This study evaluated the efficacy and safety of combining idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Methods: Using a Bayesian adaptive design, patients (pts) deemed suitable for intensive chemotherapy were randomized to receive CIA (n = 106) or FIA (n = 76). All pts received idarubicin 10 mg/m2 IV daily on Days 1-3 and cytarabine 1 g/m2 IV daily on Days 1-5. Clofarabine and fludarabine were given at 15 mg/m2 and 30 mg/m2, respectively, IV daily on Days 1-5. Pts with FLT3 mutations could receive sorafenib. Up to 6 cycles of consolidation were allowed for responding pts. Results: Baseline characteristics were similar comparing CIA to FIA with a median age of 53 years (range, 20-66) vs 49 years (range, 18-66) respectively and ELN risk intermediate-2/adverse of 57% and 58% respectively. With a median follow-up of 27 months (range, 1-58), the CIA and FIA arms had a similar CR/CRp rate (80% and 82%, respectively). MRD negativity rate by multiparameter flow cytometry at the time of CR/CRp was higher comparing CIA to FIA (80% vs. 65%, respectively, P = 0.07). The median EFS were 13 months and 12 months, respectively (P = 0.91), and the median OS were 24 months and not reached, respectively (P = 0.23). There were more adverse events (all grades) associated with CIA, particularly AST/ALT elevation (29% vs 4%), hyperbilirubinemia (26% vs 9%) and rash (31% vs 9%). Early mortality was similar in the 2 arms (60-day mortality: 4% for CIA vs 1% for FIA; P = 0.32). Comparing the 2 arms to a historical cohort of pts treated with IA showed similar response rates, EFS and OS excluding pts with FLT3 mutations from this analysis. However, in pts < 50 years of age, FIA was associated with improved survival compared with IA (2-year EFS rate: 58% vs 30%, P = 0.05; 2-year OS rate: 72% vs 36%; P = 0.009). Conclusions: CIA and FIA have similar efficacy in younger pts with newly diagnosed AML. FIA is associated with a better toxicity profile and may improve survival compared to IA in pts < 50 years of age. Clinical trial information: NCT01289457.