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Chronic Myeloproliferative Disorders

Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase

Leukemia volume 22, pages 2176–2183 (2008)Cite this article

Abstract

Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70 mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03–20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in ⩽6% of patients, except febrile neutropenia (15%). Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population.

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Acknowledgements

We acknowledge the key contributions made by the remaining primary investigators of this trial: JJ Garcia (Argentina); T Hughes, B Van Leeuwen (Australia); P Valent (Austria); G Verhoef (Belgium); CA De Souza, PE Dorlhiac-Llacer (Brazil); P Laneuville (Canada); K Porkka (Finland); G Marit, J Reiffers, F Maloisel, J-L Harrousseau (France); MC Müller (molecular analyses), T Fischer (Germany); A Nagler (Israel); F Ferrara (Italy); J-H Lee (South Korea); W Schroyens (The Netherlands); P Caguioa (Philippines); B Simonsson, M Ekblom (Sweden); A Gratwohl (Switzerland); P-M Chen (Taiwan); S Jootar (Thailand); T Holyoake (UK); A Rapoport, R Larson, C Schiffer, R Stone, A Greco, S Goldberg, K Bhalla, S Petersdorf, P Emanuel (USA). This study was supported by research funding from Bristol-Myers Squibb. Professional writing and editorial assistance, funded by Bristol-Myers Squibb, was provided by Gardiner-Caldwell US.

Author information

Authors and Affiliations

  1. Department of Leukemia,

    J Cortes

  2. MD Anderson Cancer Center, Houston, TX, USA

    J Cortes

  3. Department of Internal Medicine, St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea

    D-W Kim

  4. Department of Hematology, Hôpital Saint Louis, Centre d’Investigation Clinique, Paris, Cedex, France

    E Raffoux

  5. Institute of Hematology and Medical Oncology ‘L e A Seràgnoli’, University of Bologna, Bologna, Italy

    G Martinelli

  6. Weill Medical College, Cornell University, New York Presbyterian Hospital, New York, NY, USA

    E Ritchie

  7. Clinical Research Centre, CHU de Poitiers, Poitiers, France

    L Roy

  8. Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA

    S Coutre

  9. Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France

    S Corm

  10. Oncology and Hematology Program, Hospital Israelita Albert Einstein, Sao Paulo, Brazil

    N Hamerschlak

  11. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, China

    J-L Tang

  12. Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany

    A Hochhaus & T Ernst

  13. Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    H J Khoury

  14. Department of Oncology and Hematology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

    T H Brümmendorf

  15. Service d’Hématologie, Hôpital Edouard Herriot, Lyon Cedex, France

    M Michallet

  16. Dipartimento Di Medicina Interna II Ed Ematologia, Azienda Ospedaliera S. Luigi, Orbassano, Italy

    G Rege-Cambrin

  17. Department of Oncology, McGill University, Montreal, Canada

    C Gambacorti-Passerini

  18. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    J P Radich

  19. Bristol-Myers Squibb, Wallingford, CT, USA

    C Zhu & J M A Van Tornout

  20. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, MI, USA

    M Talpaz

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  1. J Cortes
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Corresponding author

Correspondence to J Cortes.

Additional information

Data contained within this article were presented at the American Society of Hematology Annual Meeting in Orlando, FL, 9–12 December 2006.

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Cortes, J., Kim, DW., Raffoux, E. et al. Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. Leukemia 22, 2176–2183 (2008). https://doi.org/10.1038/leu.2008.221

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  • DOI: https://doi.org/10.1038/leu.2008.221

Keywords

  • dasatinib
  • chronic myeloid leukemia
  • blast phase
  • BCR-ABL
  • SRC
  • imatinib resistance

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