CPX-351 versus cytarabine (CYT) and daunorubicin (DNR) therapy in newly diagnosed AML patients age 60-75: Safety and efficacy in secondary AML (sAML).

Abstract

6519 Background: CPX-351 encapsulates CYT and DNR at a 5:1 molar ratio predicted in vitro to maximize synergy. CPX-351 liposomes accumulate within bone marrow with preferential uptake by leukemia cells followed by intracellular release of drug. Multiple CRs in advanced AML patients in phase I led to a randomized phase IIb study comparing CPX-351 (85 pts) vs. standard CYT+DNR (7+3) (41 pts) for untreated elderly patients with AML. Trends favored CPX-351 vs. 7+3 in CR + CRi rates, 60d mortality and EFS. Significant improvement in OS was observed in the 51 (40%) patients entered with sAML (prior antecedent hematologic disorders (AHD): MDS, MPD, CMMoL and treatment-related AML (t-AML)) and this led to an analysis of this subpopulation. Methods: Previously untreated de novo or secondary AML patients, age 60-75, PS= 0-2, SCr < 2.0 mg/dL, total bilirubin <2.0 mg/dL, ALT/AST <3 x ULN, and LVEF >50% were eligible. Patients were randomized 2:1 to receive up to 2 induction and 2 consolidation courses of CPX-351 (100 u/m2; D 1, 3, 5; 90 min infusion, 1 unit= 1 mg CYT + 0.44 mg DNR) or standard 7+3 treatment (CYT=100 mg/m2 and DNR=60 mg/m2). Consolidation with hematopoietic stem cell transplantation (SCT) was permitted. Endpoints included: CR + CRi rate (1° endpoint) and duration, EFS, aplasia rate, survival at 1 year, and death at day 30 and 60. Results: 2:1 randomization assigned 32 (63%) sAML pts. to CPX-351 and 19 (37%) pts. to 7+3. Most patients (45 of 51) had AHD; only 6 of 51 had t-AML. Conclusions: CPX-351 exhibited higher response rate, lower induction mortality despite higher infection rate, and improved survival (p=0.01) among sAML patients compared to standard 7+3, providing a strong rationale for a phase III study. % As of 1 February 2011 CPX-351 n=32 7+3 n=19 Demographics Sex (male) 66 47 Race (Caucasian) 92 95 Age (median, yrs) 68 68 (>70) 41 42 ECOG PS (0-1) 78 79 (2) 22 21 Cytogenetic risk (adverse) 28 32 Prior AHD MDS 59 58 CMMoL 13 11 MPD 13 16 MDS/MPD 3 5 Prior therapy for AHD 34 37 Induction mortality (60d) 6 32 Adverse events (gr 3/4) Febrile neutropenia 56 47 Bacteremia 28 10 Pneumonia 25 10 Fungal 16 5 Sepsis 3 16 Efficacy %CR + CRi 56 32 EFS (median) 3.8m 1.4m p=0.07 OS (median) 12.1m 6.1m p=0.01