The Impact Of Hematopoietic Cell Transplantation (Hct) On Survival: An Exploratory Analysis Of A Phase 3 Study Of Cpx-351 Versus 7+3 In Older Patients With Newly Diagnosed, High-Risk/Secondary Aml (Saml)

Introduction CPX-351 (Vyxeos®), a dual-drug liposomal encapsulation of cytarabine (C) and daunorubicin (D) at a synergistic ratio, is approved by the FDA and EMA for adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. In a phase 3 study, CPX-351 significantly improved median overall survival (OS; 9.56 vs 5.95 mo; HR = 0.69 [95% CI: 0.52-0.90]; 1-sided P  = 0.003) and event-free survival (EFS; 2.53 vs 1.31 mo; HR = 0.74 [95% CI: 0.58-0.96]; 2-sided P  = 0.021), and produced a higher rate of complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CR+CRi; 47.7% vs 33.3%; 2-sided P  = 0.016) vs 7+3 in patients (pts) aged 60-75 y with newly diagnosed high-risk/sAML. The higher CR+CRi rate may contribute to a higher rate of HCT, which is a potentially curative therapy that can impact long-term survival. Objective This exploratory analysis used a time-dependent proportional hazards model to assess the impact of CPX-351 vs 7+3 on survival independent of HCT status. Methods Pts could receive up to 2 induction cycles of CPX-351 (100 units/m 2 [C 100 mg/m 2  + D 44 mg/m 2 ] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m 2 /d continuously for 7 d [2nd induction: 5 d] + D 60 mg/m 2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving CR or CRi could receive up to 2 consolidation cycles with CPX-351 (65 units/m 2 [C 65 mg/m 2  + D 29 mg/m 2 ] on Days 1 and 3) or 5+2 (as in 2nd induction). HCT was performed at the physicianu0027s discretion. Results Baseline characteristics were balanced between arms. The HCT rate was 34.0% (n = 52) with CPX-351 and 25.0% (n = 39) with 7+3. Median time to HCT was 114.5 d with CPX-351 and 113.0 d with 7+3. Median OS landmarked from the time of HCT was significantly improved with CPX-351 vs 7+3 (not reached vs 10.25 mo; HR = 0.46 [95% CI: 0.24-0.89]). When HCT was treated as a time-dependent covariate, the HRs favored CPX-351 vs 7+3 for OS and EFS (Table), suggesting CPX-351 may be associated with prolonged OS and EFS independent of HCT. The safety profile of CPX-351 was generally consistent with that of 7+3. Early mortality rates with CPX-351 and 7+3, respectively, were 5.9% and 10.6% at Day 30 and 13.7% and 21.2% at Day 60. Conclusions CPX-351 was associated with significantly longer median OS and EFS and higher rates of CR+CRi and HCT vs 7+3 in older pts with newly diagnosed high-risk/sAML. Exploratory analyses suggest CPX-351 prolonged OS and EFS independent of HCT.