AML-522 Outcomes of Patients Treated With Venetoclax-Based Combination Therapy in Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms; Real World Data from a Single Center Cohort

Abstract

The outcomes of older patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy remain poor. Addition of venetoclax (ven) to hypomethylating agents (HMA) or low dose cytarabine (LoDAC) has become the standard of care based on the VIALE-A and VIALE-C trials. We investigated outcomes of patients treated with ven-based therapy in both newly-diagnosed and R/R settings. Patients diagnosed with AML between 2/2018 and 2/2022 who completed at least one cycle of ven-based therapy at our center were included. Clinical, cytogenetic and molecular data were collected. Responses were assessed using IWG criteria. OS was calculated from venetoclax initiation and estimated using Kaplan-Meier method. Multivariable cox-regression was used to assess factors associated with response. Sixty-nine patients completed at least one cycle of ven-based therapy for AML at our center. Median age at diagnosis was 71 (28-88 years) and 35 (51%) patients were female. Majority (76.8%) of patients had high risk disease per ELN stratification. Five (7%) of patients had high grade myeloid neoplasms. Majority of patients received ven in combination with HMA (81.%). CR/CRi/CRh rate was 44.9% and ORR 78.3%. Twenty-one (30%) proceeded with transplant. In univariate analyses for response, ELN cytogenetic risk (p<.001), FLT3-ITD (p=.016), IDH1/2 (p=.004) were associated with response, with a trend for significance for NPM1 mutation (p=.067). Looking at survival analyses, de-novo AML (vs t-AML or secondary AML) (p=.012) and achieving CR within two cycles of therapy (p<.001) were associated with improved OS, but not diagnosis status [i.e., new vs R/R setting] (p=NS) or prior HMA use (p= NS). This study of real-world outcomes with ven-based therapy in AML assessed factors predictive of treatment response and OS. ELN cytogenetic risk was associated with response and OS. Patients with therapy-related or secondary AML had poorer OS vs de novo disease. Patients with new vs R/R disease had similar outcomes, likely due to the fact that the majority of patients had high risk ELN disease risk. Our observations highlight the clinical potential of ven-based therapy for R/R AML and the need for more robust trial data including patients with R/R disease.