CPX-351 vs Intensive Chemotherapy in Patients With de Novo Intermediate or Adverse Risk AML Stratified by Genomics

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by clonal expansion of myeloid blasts. Interestingly comparing de novo and stringently defined secondary AMLs occurring after a documented phase of MDS, Lindsley et al. could identify among de novo AMLs a molecular subgroup, termed 'secondary-type AML', defined by mutations in either SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR and/or STAG2 genes. Among de novo AML patients, 33.3% had secondary-type mutations. It has been shown that patients older than 60 years of age harboring secondary-type AML, as defined by this 8-gene molecular signature, had inferior outcome to those without 'secondary-type' mutations when treated with conventional 7+3 chemotherapy, combining cytarabine and an anthracycline (ALFA 1200 study). This was notably true among patients with 'intermediate-risk' disease per European LeukemiaNet criteria. The incidence of 'secondary-type' AML mutations increases with age and with cytogenetic risk category. Notably, roughly 50% of de novo AML patients with intermediate risk older than 50 years of age harbor such secondary-type mutations, New therapeutic options are thus necessary in patients older than 50 years with de novo AML classified adverse risk but also intermediate risk and associated to secondary-type mutation This study will evaluate the rate of MRD negative remissions with CPX-351 used as induction and consolidation therapy according to its marketing authorization (AMM), as compared to intensive chemotherapy in a population of non-MRC AMLs enriched in secondary-like mutations. In addition,P-gp activity will be explore as a putative biomarker. Duration of the enrollment period: 36 months Duration of treatment: 6 months Duration of the participation for a patient: 18 months (post randomization) (including approximately 6 months treatment, and 12 months of post-treatment follow up) Overall duration of the study: 58 months including the analysis of the results