Real-World Outcomes in First-Line Venetoclax-Based Therapy in Patients With AML Ineligible for Intensive Chemotherapy: A Single Center Study.

BACKGROUND: VIALE-A established azacitidine and venetoclax as first-line therapy for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. However, real-world use of venetoclax often differs from clinical trial protocols. PATIENTS AND METHODS: We conducted a single-center retrospective study of 160 AML patients treated with first-line venetoclax-based therapy to investigate how cycle 1 venetoclax exposure, characterized by treatment duration and dose (adjusted for CYP3A inhibitor use), is associated with treatment outcomes. RESULTS: The composite complete response (CRc) rate was 55% overall, and 66% among patients with an evaluable bone marrow biopsy, with a median time to CRc of 41.5 days. Patients receiving 21 ± 3 days of venetoclax in cycle 1 demonstrated higher CRc rates and shorter time to CRc compared with those receiving the standard 28 days, while greater venetoclax dose or exposure in cycle 1 was not associated with improved outcomes. Hematologic adverse events requiring treatment modification were significantly associated with the achievement of CRc (P < .001). Cycle 1 venetoclax exposure did not correlate with subsequent treatment duration. CONCLUSION: These findings suggest that increased early venetoclax exposure was not associated with improved clinical outcomes in this real-world cohort; however, prospective studies are needed to validate these observations and inform optimization of venetoclax dosing strategies in real-world practice.