Hematol Oncol

CPX-351, a liposomal formulation of cytarabine and daunorubicin, has been approved patients with secondary/high-risk acute myeloid leukemia including therapy-related acute myeloid leukemia or AML with myelodysplasia-related changes according to the WHO 2016 classification. The aim of this study was to determine the efficacy and safety of CPX-351 in 283 patients with AML registered in the PETHEMA database. Evolving outcome results were analyzed comparing early treated patients (before-2022, N=147) with those treated after Spanish financial approval (since-2022, N=136). The CR/CRi rate was 54% in the overall cohort, without significant differences comparing both time periods. By contrast, early death rates at day + 30 and day + 60 were higher in early period patients (11.6 vs. 5.1% and 17 vs. 8.1%, p=0.03 and p=0.031). Consequently, more patients could undergo HSCT in the latter treatment period (33.8% vs. 25.2%, p=0.04). Patients treated with CPX-351 since 2022 showed a significantly higher unadjusted 2-year OS probability compared with patients treated earlier [40.3% (95% CI: 26.3-62.4) versus 25.2% (95% CI: 18.6-34.1), P=0.017]. However, treatment period was not independently associated with OS in multivariable analysis. Only TP53 wild-type status [HR 0.51 (95% CI: 0.25-1.05)] and achievement of MRD negativity after induction [HR 0.54 (95% CI: 0.29-1.0)] remained independently associated with improved OS. Overall, outcomes after CPX-351 appeared to improve over time in unadjusted analyses; however, the absence of an independent effect of treatment period and differences in patient selection between periods preclude attributing this improvement specifically to a temporal learning effect.