Venetoclax plus daunorubicin and cytarabine for newly diagnosed acute myeloid leukemia: results of a phase 1b study

Author(s): Ioannis Mantzaris1; Mendel Goldfinger1; Matan Uriel1; Aditi Shastri1,2; Nishi Shah1; Kira Gritsman1,3; Noah S. Kornblum1; Lauren Shapiro1; Roberto Alejandro Sica1; Anne Munoz1; Nicole Chambers1; Aradhika Dhawan1; Jhannine Alyssa Verceles1; Karen Fehn1; Balda Tirone1; Lamisha Shah3; Shaunmonique Clark1; Chenxin Zhang4; Mimi Kim4; Dennis L. Cooper1; Amit Verma1,2; Marina Konopleva1,5; Eric J. Feldman1
Source: https://doi.org/10.1182/blood.2024026700
Original Article
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Venetoclax in addition to 7+3 regimens improved response rate and there were no induction deaths when studied in 34 patients. Complete response (CR) was achieved in 85.3% of patients and 86.2% were negative for measurable residual disease (MRD).

ABSTRACT

Venetoclax (Ven), when 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, we assessed the safety and efficacy of Ven with daunorubicin and cytarabine in patients with newly diagnosed AML. A total of 34 patients (median age, 59 years; 62% non-White) received Ven at escalating durations (8, 11, or 14 days). Adverse events included febrile neutropenia (100%), sepsis (29%), and enterocolitis (23.5%), but there were no induction deaths. The median recovery times for neutrophils (>1.0 × 103/μL) and platelets (>100 × 103/μL) were less than 30 days. Composite complete remission was achieved in 85.3% of patients, and 86.2% were negative for measurable residual disease (MRD). Responses spanned all European Leukemia Net 2022 risk categories. With a median follow-up of 9.6 (2-20) months, the median duration of response, event-free survival, and overall survival were not reached. Ven (400 mg), when 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. This trial was registered at clinicaltrials.gov as #NCT05342584.

Author Affiliations

1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY;2Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY;3Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY;4Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY;5Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY

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