Intensive Induction Chemotherapy Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in NPM1-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study

Introduction: Intensive induction chemotherapy (IC) with cytarabine + anthracycline remains the standard of care for younger and fit patients (pts) with acute myeloid leukemia (AML). Post-hoc analyses from clinical trials evaluating venetoclax (VEN)-based therapies in AML have identified mutations in NPM1 as being associated with high rates of durable responses. However, these trials were conducted in pts age ≥75 years or unfit for IC. Thus, it is unknown whether IC or hypomethylating agent (HMA)+VEN is the optimal frontline treatment for pts with NPM1-mutant AML. We performed a large multicenter retrospective cohort study dedicated to pts with newly diagnosed AML with NPM1 mutations, comparing treatment modalities and assessing the impact of clinical and molecular characteristics on response and survival. Methods: We included pts with newly diagnosed, NPM1-mutant AML who were treated at 4 large academic centers with IC (either conventional 7+3 or liposomal cytarabine/daunorubicin [CPX-351]) or HMA+VEN. Detection of NPM1 mutations was performed at the participating sites either by polymerase chain reaction (PCR) or next-generation sequencing (NGS) per local standards. Composite complete response (cCR) was defined as complete response (CR) + CRi (CR with incomplete count recovery) per European LeukemiaNet 2017 criteria. Overall survival (OS) was compared between groups by log-rank test. Cox regression multivariable model for OS was fitted using a stepwise backward selection to evaluate the effect of treatment, allogeneic stem cell transplantation (allo-SCT) as a time-varying covariate and additional covariates with a p