Initial salvage therapy in first relapse AML: A phase IIb study of CPX-351 versus investigator’s choice—A subset analysis by prognostic group.

Abstract

6525 Background: CPX-351 encapsulates cytarabine and daunorubicin within liposomes at a 5:1 molar ratio, shown in vitro to maximize synergy. Liposomal encapsulation enables preferential uptake of drug within leukemic blasts followed by intracellular release enhancing efficacy in AML. A randomized Phase 2b study in 1st relapse AML completed 1-year follow up with improvement in event free (EFS) and overall survival (OS). This report describes patient outcomes with a focus on the unfavorable subset per the European Prognostic Index (EPI) (Breems DA, et al. J Clin Oncol, 2005 Mar 20;23:1969-1978). Methods: Patients (pts) ≤65yo in 1st relapse AML after an initial CR >1 month, ECOG PS= 0-2, serum creatinine< 2.0 mg/dL, total bilirubin < 2.0 mg/dL, ALT/AST < 3 x ULN, and LVEF >50% were eligible. Pts with APL, daunorubicin exposure >368 mg/m2 (or other anthracycline equivalent), active CNS leukemia, uncontrolled infections were excluded. Pts were randomized 2:1 to receive up to 2 inductions and 2 consolidation courses of CPX-351 (100 u/m2; D 1, 3, 5) or investigators choice of intensive salvage treatment. Post remission allo-transplantation was permitted. 126 pts were stratified by EPI into favorable, intermediate, and unfavorable groups (with projected 1-year OS of 70%, 49%, and 16%). The primary efficacy endpoint was % survival at 1-year. Results: CPX-351 increased the rate of morphologic leukemia-free state (77% vs. 60%), the rate of CR + CRi (51% vs. 41%), and the median EFS (4.0 vs. 1.4 mo) and OS (8.5 vs. 6.3 mo) in the overall patient population. Significant survival improvement occurred amongst those with unfavorable EPI scores (HR=0.55, p-value=0.02) with improved 1-year survival (29% vs. 10%). CPX-351 treatment resulted in more prolonged cytopenias with increased febrile neutropenia and grade 3-4 infections, but not in the D 60 mortality (overall: 15% vs. 16%; unfavorable: 16% vs. 24%). Conclusions: CPX-351 is highly active in AML and induces remission even in patients with prior cytarabine and anthracycline exposure. Efficacy was evident in every prognostic group, particularly in the unfavorable EPI group where a statistically significant improvement in 1-year survival was observed.