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

Autor:	DiNardo CD; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX., Pratz K; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD., Pullarkat V; Department of Hematology and Hematopoietic Cell Transplantation and.; Gehr Family Center for Leukemia Research, City of Hope National Medical Center, Duarte, CA., Jonas BA; University of California Davis Comprehensive Cancer Center, Sacramento, CA., Arellano M; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Becker PS; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle, WA., Frankfurt O; Northwestern University Feinberg School of Medicine, Chicago, IL., Konopleva M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX., Wei AH; The Alfred Hospital and Monash University, Melbourne, Australia., Kantarjian HM; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX., Xu T; AbbVie Inc., North Chicago, IL., Hong WJ; Genentech, San Francisco, CA., Chyla B; AbbVie Inc., North Chicago, IL., Potluri J; AbbVie Inc., North Chicago, IL., Pollyea DA; Blood Cancer and Bone Marrow Transplant Program, University of Colorado School of Medicine, Aurora, CO; and., Letai A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2019 Jan 03; Vol. 133 (1), pp. 7-17. Date of Electronic Publication: 2018 Oct 25.
DOI:	10.1182/blood-2018-08-868752
Abstrakt:	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/m 2 , days 1-5, intravenously [IV]) or azacitidine (75 mg/m 2 , 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). (© 2019 by The American Society of Hematology.)
Databáze:	MEDLINE
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