Venetoclax plus Daunorubicin and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia: Results of a Phase 1b Study

• Ven can be safely used in combination with “7+3” chemotherapy for remission induction in newly diagnosed AML patients.

• Ven plus “7+3” led to high rates of measurable residual disease-negative complete remission.

Venetoclax combined with intensive chemotherapy shows promise for untreated acute myeloid leukemia (AML), but its integration with the '7+3' regimen remains underexplored. In a phase 1b study (NCT05342584), we assessed the safety and efficacy of venetoclax with daunorubicin and cytarabine in newly diagnosed AML patients. Thirty-four patients (median age 59 years; 62% non-white) received venetoclax at escalating durations (8, 11, or 14 days). Adverse events included febrile neutropenia (100%), sepsis (29%), and enterocolitis (23.5%), with no induction deaths. Median recovery times for neutrophils (>1.0K/uL) and platelets (>100K/uL) were under 30 days. Composite complete remission (CRc) was achieved in 85.3% of patients, with 86.2% being measurable residual disease (MRD)-negative. Responses spanned all ELN2022 risk categories. With a median follow-up of 9.6 (2-20) months, median duration of response, event-free survival and overall survival were not reached. Venetoclax (400 mg) combined with '7+3' chemotherapy was safe and effective in achieving MRD-negative remissions across all durations. Ven dose optimization is being explored in the expansion phase of this trial. Future multicenter studies should confirm our findings.