Efficacy and Safety of CPX-351 Versus 7+3 in a Phase 3 Exploratory Analysis in Patients with High-Risk/Secondary Acute Myeloid Leukemia (sAML) with Prior Hypomethylating Agent (HMA) Exposure Who Achieved Remission

Introduction Patients (pts) with newly diagnosed sAML may have previously received HMA therapy for an antecedent hematologic malignancy (eg, myelodysplastic syndrome [MDS]). Outcomes for pts with MDS who progress following HMA therapy are typically poor, with remission rates Objective An exploratory subgroup analysis of the phase 3 study was performed to compare outcomes in pts with any prior HMA exposure who achieved complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi). Methods Pts were randomized 1:1 to receive 1-2 induction cycles with CPX-351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] as a 90-min infusion on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d [2nd induction: 5 d] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving CR+CRi could receive up to 2 consolidation cycles with CPX-351 (65 units/m2 [C 65 mg/m2 + D 29 mg/m2] on Days 1 and 3) or 5+2 (as in 2nd induction). Pts could receive hematopoietic cell transplantation (HCT) at the physician's discretion. Results Of 309 pts enrolled, 133 (43%) had received prior HMAs; Of these, 23/62 (37%) receiving CPX-351 and 20/71 (28%) receiving 7+3 achieved CR+CRi (odds ratio [OR] = 1.50 [95% CI: 0.73-3.12]) and were included in this analysis. Baseline characteristics were balanced between treatment arms. In pts with prior HMAs who achieved CR+CRi, median OS was longer with CPX-351 (Figure 1). Of note, median OS was also longer with CPX-351 (26.32 vs 10.43 months) in pts without prior HMAs. More pts with prior HMAs who achieved CR+CRi with CPX-351 vs 7+3 underwent HCT (57% vs 35%; relative risk = 1.39 [95% CI: 0.73-2.67]), and OS landmarked from the HCT date was longer with CPX-351 vs 7+3 (Figure 2). The safety profile was generally comparable between treatment arms in pts with prior HMAs who achieved CR+CRi. The most common serious treatment-emergent adverse events were febrile neutropenia (CPX-351: 13%; 7+3: 10%), ejection fraction decreased (9%; 10%), and subdural hemorrhage (0%; 10%). There was no early mortality by Day 60 in either arm. Conclusions Among pts who had prior HMA exposure and achieved CR+CRi, CPX-351 improved median OS, the rate of HCT, and median OS landmarked from the HCT date vs 7+3. The CPX-351 safety profile in this subgroup was consistent with the overall study population and the known profile of 7+3.