This study evaluated the efficacy and safety of combining idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed acute myeloid leukemia (AML). Eligible patients were randomized to receive CIA (n = 106) or FIA (n = 76). All patients received idarubicin 10 mg/m2 intravenously (IV) daily on days 1 through 3, and cytarabine 1 g/m2 IV daily on days 1 through 5. CIA and FIA were given at 15 mg/m2 IV daily and 30 mg/m2 IV daily, respectively, on days 1 through 5. Patients with FLT3 mutations were eligible to receive sorafenib.
Baseline characteristics were similar for the CIA and FIA arms, and median follow-up was 27 months. The CIA and FIA groups had a similar rate of complete remission (CR) or CR with incomplete platelet recovery (80% and 82%, respectively). Median event-free survival rates were also similar for the 2 groups (13 months and 12 months, respectively [P = 0.91]); median overall survival (OS) was 24 months for the CIA arm and was not reached in the FIA arm (P = 0.23). However, the minimal residual disease negativity rate (as measured by multiparameter flow cytometry) at the time of CR was higher for CIA than for FIA (80% vs 65%, respectively; P = 0.07). There were more adverse events associated with CIA, including AST/ALT elevation (29% vs 4%), hyperbilirubinemia (26% vs 9%), and rash (29% vs 12%). When the 2 arms were compared with a historical cohort of patients treated with idarubicin and cytarabine, FIA was associated with improved 2-year OS (72% vs 36%; P = 0.009) in patients aged <50 years.
The findings indicate that CIA and FIA have similar efficacy in younger patients with newly diagnosed AML. However, FIA is associated with a better toxicity profile and may improve survival compared with idarubicin and cytarabine in patients aged <50 years.
Issa GC, et al. ASCO Abstract 7037.