Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: A multicentric French cohort

Abstract

CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML).We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profilewas observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD,1023 was achieved in 57% of complete response (CR)/CR with incomplete hematological recovery (CRi) patients. Only the presence of mutated TP53 (P 5.02) or PTPN11 (P 5.004) predicted lower response in multivariate analysis. Interestingly, high-risk molecular prognosis subgroups defined by 2017 European LeukemiaNet risk stratification, including ASXL1 and RUNX1 mutations, were not associated with a significantly lower response rate using CPX-351. With amedian follow-up of 8.6 months, median overall survival (OS) was 16.1 months. Thirty-six patients underwent allogeneic stem cell transplantation with a significantly longer median OS compared with nontransplanted patients (P,.001). In multivariate analyses, only spliceosome mutations were associated with better OS (P5.04). In comparisonwith intensive chemotherapy, there was no difference in OS for patients,60 years. These data confirm the efficacy and safety of CPX-351 in high-risk AML(t-AML and MRC-AML) in a real-life setting. CPX-351 is a treatment of choice for patients aged $60 years.