Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Courtney D DiNardo  1 , Keith Pratz  2 , Vinod Pullarkat  3   4 , Brian A Jonas  5 , Martha Arellano  6 , Pamela S Becker  7   8 , Olga Frankfurt  9 , Marina Konopleva  1 , Andrew H Wei  10 , Hagop M Kantarjian  1 , Tu Xu  11 , Wan-Jen Hong  12 , Brenda Chyla  11 , Jalaja Potluri  11 , Daniel A Pollyea  13 , Anthony Letai  14
Affiliations

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

Courtney D DiNardo et al. Blood. .

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).

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: C.D.D. received research funding from AbbVie/Genentech, Agios, Celgene, Daiichi Sankyo, Millennium, and Novartis and served as consultant for Agios, and an advisory board member for AbbVie, Agios, Bayer, Celgene, Karyopharm, and Medimmune; K.P. received research funding from AbbVie, Agios, Daiichi Sankyo, and Millennium and is an advisory board member for AbbVie, Astellas, and Boston BioMedical; B.A.J. served as consultant for AbbVie, Amgen, and Tolero and as an advisory board member for Celgene and received research funding to his institution from AbbVie, Incyte, Forma, Celgene, Daiichi Sankyo, Pharmacyclics, Genentech/Roche, Glycomimetics, AROG, Accelerated Medical Diagnostics, LP Therapeutics, Esanex, and Kalobios; M.A. received research funding from Cephalon Oncology; P.S.B. received research funding from AbbVie, Bristol-Myers Squibb, Glycomimetics, JW Pharmaceutical, Amgen, Novartis, Trovagene, Trethera, and Aptose and served as an advisory board member for Pfizer and CVS Caremark; O.F. served on an advisory board and speakers’ bureau for Celgene, Aggios, and Jazz and as n advisory board member for AbbVie; M.K. served as a consultant for AbbVie, Genentech, and F. Hoffman La-Roche and as an advisory board member for F. Hoffman La-Roche and holds shares from Reata Pharmaceuticals and received honoraria from Amgen, Abbvie, and Genentech and research funding from AbbVie, Genentech, Eli Lilly, Cellectis, Calithera, Stemline, Threshold, Flexus Biosciences, Novartis, Ablynx, and Agios; A.H.W. served in an advisory role for AbbVie, Celgene, Novartis, Amgen, and Servier and received research funding from AbbVie, Celgene, and Servier and honoraria from AbbVie, Celgene, Novartis, Amgen, and Servier; H.M.K. received honoraria from AbbVie, Actinium, Agios, Amgen, Immunogen, Orsinex, Pfizer, and Takeda and research grants from AbbVie, Agios, Amgen, Ariad, Astex, Bristol-Myers Squibb, Cyclacel, Immunogen, Jazz, and Pfizer; T.X. is an employee of AbbVie and may hold stock or stock options; W.-J.H. is an employee of Genentech and may hold stock or stock options; B.C. is an employee of AbbVie and may hold stock or stock options; J.P. is an employee of AbbVie and may hold stock or stock options; D.A.P. serves on the data safety monitoring board for GlycoMimetics and as an advisory board member for Pfizer, Jazz, Takeda, Curis, Argenx, Agios, Servier, Celgene, and AbbVie and received research funding from AbbVie, Celgene, and Pfizer; and A.L. serves as a consultant for and receives research funding from AbbVie, TetraLogic, AstraZeneca, and Novartis and is a cofounder of Flash Therapeutics and Vivid Bioscience. V.P. declares no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Duration of CR + CRi by venetoclax dose levels (dose escalation + dose expansion cohorts). CR + CRi duration for all patients on study (black), the venetoclax 400 mg cohort (orange), the venetoclax 800 mg cohort (green), and the venetoclax 1200 mg cohort (blue). VEN, venetoclax.
Figure 2.
Figure 2.
OS by venetoclax dose levels (dose escalation + dose expansion cohorts). OS for all study patients (black), the venetoclax 400-mg cohort (orange), the venetoclax 800-mg cohort (green), and the venetoclax 1200-mg cohort (blue).
See this image and copyright information in PMC

Comment in

References

    1. Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7. - PMC - PubMed
    1. Krug U, Büchner T, Berdel WE, Müller-Tidow C. The treatment of elderly patients with acute myeloid leukemia. Dtsch Arztebl Int. 2011;108(51-52):863-870. - PMC - PubMed
    1. Pettit K, Odenike O. Defining and treating older adults with acute myeloid leukemia who are ineligible for intensive therapies. Front Oncol. 2015;5:280. - PMC - PubMed
    1. Kantarjian H, Ravandi F, O’Brien S, et al. . Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116(22):4422-4429. - PMC - PubMed
    1. Kantarjian H, O’brien S, Cortes J, et al. . Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106(5):1090-1098. - PubMed

Publication types

Associated data