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Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia.

Author information

1
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
2
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
3
Department of Hematology and Hematopoietic Cell Transplantation and.
4
Gehr Family Center for Leukemia Research, City of Hope National Medical Center, Duarte, CA.
5
University of California Davis Comprehensive Cancer Center, Sacramento, CA.
6
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA.
7
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
8
Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
9
Northwestern University Feinberg School of Medicine, Chicago, IL.
10
The Alfred Hospital and Monash University, Melbourne, Australia.
11
AbbVie Inc., North Chicago, IL.
12
Genentech, San Francisco, CA.
13
Blood Cancer and Bone Marrow Transplant Program, University of Colorado School of Medicine, Aurora, CO; and.
14
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Abstract

Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. B-cell lymphoma 2 (BCL-2) overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study. Patients (N = 145) were at least 65 years old with treatment-naive AML and were ineligible for intensive chemotherapy. During dose escalation, oral venetoclax was administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1-5, intravenously [IV]) or azacitidine (75 mg/m2, days 1-7, IV or subcutaneously). In the expansion, 400 or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was 74 years, with poor-risk cytogenetics in 49% of patients. Common adverse events (>30%) included nausea, diarrhea, constipation, febrile neutropenia, fatigue, hypokalemia, decreased appetite, and decreased white blood cell count. No tumor lysis syndrome was observed. With a median time on study of 8.9 months, 67% of patients (all doses) achieved complete remission (CR) + CR with incomplete count recovery (CRi), with a CR + CRi rate of 73% in the venetoclax 400 mg + HMA cohort. Patients with poor-risk cytogenetics and those at least 75 years old had CR + CRi rates of 60% and 65%, respectively. The median duration of CR + CRi (all patients) was 11.3 months, and median overall survival (mOS) was 17.5 months; mOS has not been reached for the 400-mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML (This trial was registered at www.clinicaltrials.gov as #NCT02203773).

PMID:
30361262
PMCID:
PMC6318429
DOI:
10.1182/blood-2018-08-868752
[Indexed for MEDLINE]
Free PMC Article

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