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Acute myeloid leukemia

Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission: a phase 2 Cancer and Leukemia Group B Study (CALGB 10503)

Leukemia volume 31, pages 34–39 (2017)Cite this article

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Abstract

In this prospective phase 2 clinical trial conducted by Cancer and Leukemia Group B (CALGB, now the Alliance), we studied decitabine as maintenance therapy for younger adults with acute myeloid leukemia (AML) who remained in first complete remission (CR1) following intensive induction and consolidation. Given that decitabine is clinically active in AML and with hypomethylating activity distinct from cytotoxic chemotherapy, we hypothesized that 1 year of maintenance therapy would improve disease-free survival (DFS) for AML patients <60 years, who did not receive allogeneic stem cell transplantation in CR1. After blood count recovery from final consolidation, patients received decitabine at 20 mg/m2 intravenously daily for 4–5 days, every 6 weeks for eight cycles. One hundred and thirty-four patients received decitabine and 85 (63%) had favorable risk AML. The median number of cycles received was 7 (range: 1–8) and the primary reason for discontinuation was relapse. DFS at 1 year and 3 years was 79% and 54%, respectively. These results are similar to the outcomes in the historical control comprising similar patients treated on recent CALGB trials. Thus, maintenance with decitabine provided no benefit overall. Standard use of decitabine maintenance in younger AML patients in CR1 is not warranted. This trial was registered at www.clinicaltrials.gov as NCT00416598.

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Acknowledgements

We thank patients and their families, collaborators and staff in the CALGB and Alliance member institutions/data center and the Alliance Leukemia Tissue Bank/Ms Donna Bucci. We also thank John C Byrd, MD, and the team in the Leukemia and Leukemia Correlative Science Committees for the Alliance for review of the manuscript and assistance with molecular data. This trial was sponsored by the NCI Cancer Therapy Evaluation Program. We gratefully acknowledge the enormous contributions to this study and to the field of medicine by our friend Dr Meir Wetzler (deceased February 2015). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA31946, U10CA33601 (to CALGB), U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), and NIH/NCI K23CA120708. Additional support was provided under CA140158, CA016058, CA180850, CA101140 and CA128377. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author contributions

WB was the Study Chair of the clinical trial. RAL was the Chair of the Leukemia Committee for the Alliance (formerly CALGB). GM also assisted in the design of the study. WB, RK, DJD, GU, BLP, WS, MRB, JEK, ESW, GM, RMS and RAL enrolled patients, provided clinical management and facilitated the conduct of the study. SG, BLS and JK provided statistical support. EH and BLS managed the database. WB and RK audited the data case report forms. CDB provided support and oversight for molecular studies. KM assisted with data acquisition and interpretation, manuscript writing and formatting. All authors reviewed the results and approved manuscript submission.

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Authors and Affiliations

  1. Division of Hematology and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    W Blum, R Klisovic, K Mrózek, J Kohlschmidt & C D Bloomfield

  2. The Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA

    B L Sanford, E Hoke & J Kohlschmidt

  3. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA

    D J DeAngelo & R M Stone

  4. Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA

    G Uy

  5. Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA

    B L Powell

  6. Department of Medicine, University of Chicago, Chicago, IL, USA

    W Stock & R A Larson

  7. Department of Medicine and Greenebaum Cancer Center University of Maryland, Baltimore, MD, USA

    M R Baer

  8. Hofstra North Shore-Long Island Jewish School of Medicine, Manhasset, NY, USA

    J E Kolitz

  9. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    E S Wang

  10. Health Informatics Institute, University of South Florida, Tampa, FL, USA

    S Geyer

  11. Gehr Family Leukemia Center, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    G Marcucci

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  1. W Blum
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Correspondence to W Blum.

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Preliminary results of this manuscript were presented at the 54th Annual Meeting of the American Society of Hematology, Atlanta, GA, 9 December 2012.

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Blum, W., Sanford, B., Klisovic, R. et al. Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission: a phase 2 Cancer and Leukemia Group B Study (CALGB 10503). Leukemia 31, 34–39 (2017). https://doi.org/10.1038/leu.2016.252

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