Venetoclax plus daunorubicin and cytarabine for newly diagnosed acute myeloid leukemia: results of a phase 1b study
Abstract
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.
Article Details
Authors (23)
Ioannis Mantzaris
1Montefiore Medical Center, Bronx, United States
Mendel Goldfinger
2Montefiore Einstein Comprehensive Cancer Center, Bronx, United States
Matan Uriel
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Aditi Shastri
Nishi Shah
2Winship Cancer Institute of Emory University, Atlanta, United States
Kira Gritsman
Noah S. Kornblum
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Lauren Shapiro
Tulane University, New Orleans, Louisiana, United States
Roberto Alejandro Sica
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Anne Munoz
2Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, United States
Nicole Chambers
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Aradhika Dhawan
2Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, United States
Jhannine Alyssa Verceles
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Karen Fehn
2Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, United States
Balda Tirone
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Lamisha Shah
21Montefiore Medical Center, Department of Oncology, New York, United States
Shaunmonique Clark
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Chenxin Zhang
Mimi Kim
Dennis L. Cooper
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Amit Verma
Marina Konopleva
Eric J. Feldman
1Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY