AML-284: Venetoclax-Based vs 7+3 Induction Therapy in Fit Younger Adults With Newly Diagnosed Non-CBF AML

Venetoclax-based regimens are standard frontline treatment for newly diagnosed AML in patients who are ineligible for intensive chemotherapy due to age or comorbidities. However, their role in younger, medically fit patients remains under investigation. Previous data suggest that certain AML subtypes, particularly core binding factor (CBF) AML, may respond less favorably to venetoclaxbased therapy than intensive induction regimens. Nevertheless, headto-head comparative data are limited evaluating outcomes between venetoclax-based approaches and standard 7+3 chemotherapy in fit, non-CBFAML patients. To compare clinical outcomes of fit, younger adults with newly diagnosed non-CBF AML who received induction therapy with either venetoclax-based regimens or standard 7+3 chemotherapy. This retrospective cohort study was conducted at the RM Gorbacheva Research Institute, focusing on patients assessed for eligibility for allo-HSCT between June 2020 and August 2024. Patients were <60 years of age with non-CBF AML and an HCT-CI score of ≤2. Treatment groups received standard 7+3 chemotherapy or venetoclax in combination with HMAs or LDAC. Remission outcomes were defined per ELN criteria, including complete remission (CR), CR with partial hematologic recovery, or morphological leukemia-free state. Patients not achieving remission after 2 induction cycles were categorized as refractory. Survival metrics included overall survival (OS), event-free survival (EFS), and non-relapse mortality (NRM). Relapse was identified as ≥5% blasts in blood or bone marrow, or presence of extramedullary disease. Statistical analyses used the Kaplan-Meier method and log-rank test for survival, and Gray's test for cumulative incidence of relapse and NRM, using R version 4.4.2. 112 patients were analyzed; 72 (64.3%) received 7+3 and 40 (35.7%) received venetoclax-based regimens. After matching, both treatment groups consisted of 26 patients with comparable baseline characteristics. Venetoclax-based induction therapy demonstrated comparable OS and EFS to standard 7+3 chemotherapy. While venetoclax-treated patients exhibited a numerically higher relapse incidence, this difference did not reach statistical significance. Conversely, those receiving 7+3 experienced significantly greater NRM. Venetoclax-based therapy was associated with lower induction-related mortality and a higher rate of refractory disease, underscoring the distinct response dynamics of these regimens. These findings highlight the nuanced risk-benefit profiles of venetoclax and intensive chemotherapy, underscoring the need for further prospective validation to optimize treatment strategies and selection criteria.