Venetoclax and Azacitidine for Molecular Relapse during First Line Intensive Chemotherapy in Patients with NPM1 Mutated or Core Binding Factor (CBF) AML. a Study from the Dataml Registry

Introduction: Molecular follow-up (FU) for AML patients (pts) with NPM1 mutation, RUNX1::RUNX1T1 or CBFB::MYH11 fusion transcripts has been established over the last ten years. Real-time quantitative PCR (qPCR) is the gold standard for the evaluation of measurable residual disease (MRD) in pts undergoing intensive chemotherapy (IC). Failure to achieve a deep molecular response is a strong predictive factor of relapse and survival and may guide post remission therapy (Ivey A, NEJM 2016). Moreover, the ELN MRD working party recommended a schedule for molecular FU and recently established a definition of molecular relapse (Heuser M, Blood 2021). However, there is no therapeutic consensus for pts with molecular relapse before overt clinical relapse. Frontline allogeneic hematopoietic cell transplantation (alloHCT), salvage IC or even waiting for morphological relapse in order to screen molecular characteristics of the relapsing disease or propose a clinical trial, may be discussed with pts. Venetoclax with azacitidine (VEN/AZA) was recently approved in unfit AML pts and demonstrated a particular efficacy in NPM1-mutated AML. In this study, we thought to describe the safety and efficacy of VEN/AZA in pts with NPM1 mutated or CBF AML in molecular relapse after first line IC.