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Chronic Myeloproliferative Disorders

Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib

Leukemia volume 22, pages 1200–1206 (2008)Cite this article

Abstract

Dasatinib, a potent inhibitor of BCR–ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1–18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.

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Acknowledgements

In addition to the authors, the following primary investigators also participated in this trial: Australia: C Arthur, S Branford (molecular analyses), A Grigg, J Seymour and K Taylor; Austria: P Valent; Belgium: A Bosly; Canada: D Forrest, C Gambacorti-Passerini and P Laneuville; Denmark: JL Nielsen; Finland: K Porkka; France: J-L Harrousseau, F Maloisel, M Michallet, J Reiffers and P Rousselot; Germany: C Bokemeyer, P Erben (molecular analyses) and T Fischer; Ireland: E Conneally and M O’Dwyer; Israel: A Nagler; Italy: E Abruzzese, F Castagnetti, F Ferrara, G Lambertenghi, V Liso, G Rosti, B Rotoli and G Saglio; Korea: D-W Kim; Netherlands: J Cornelissen and AVMB Schattenberg; Peru: J Navarro; Singapore: YT Goh; Spain: J Odriozola and JL Steegmann; Sweden: M Ekblom, B Markevarn, B Simonsson and L Stenke; Switzerland: A Gratwohl; UK: T Holyoake; USA: K Bhalla, S Bilgrami, B Cheson, R Collins, S Coutre, J Dipersio, S Durham, L Fehrenbacher, JK Giguere, FA Greco, HJ Khoury, M Lilly, J Lister, S Luger, A Maniam, J McGuirk, E Merriam, MS Murali, J Radich (molecular analyses), A Rapoport, CE Rivera, C Schiffer, R Strair and M Talpaz. Professional writing and editorial assistance, funded by Bristol–Myers Squibb, was provided by Josh Collis and Andrew Richardson. The funding for this trial was provided by Bristol–Myers Squibb.

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Authors and Affiliations

  1. III Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany

    A Hochhaus & M C Müller

  2. Department of Hematology–Oncology ‘L and A Seràgnoli,’ S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    M Baccarani

  3. OHSU Cancer Institute, Oregon Health & Science University, Portland, OR, USA

    M Deininger

  4. Department of Haematology, Hammersmith Hospital, Imperial College, London, UK

    J F Apperley

  5. Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Ontario, Canada

    J H Lipton

  6. The Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA

    S L Goldberg

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

    S Corm

  8. Division of Hematology/Oncology, San Francisco School of Medicine, University of California, San Francisco, CA, USA

    N P Shah

  9. Department of Hematology, Hospital Clinic i Provincial, Barcelona, Spain

    F Cervantes

  10. Division of Hematology/Oncology, New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY, USA

    R T Silver

  11. Department of Hematology, Oncology and Coagulation, University of Leipzig, Leipzig, Germany

    D Niederwieser

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

    R M Stone

  13. Service Clinique des Maladies du Sang, Hôpital Saint-Louis, Paris, France

    H Dombret

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

    R A Larson

  15. Clinical Research Center, CHU de Poitiers, Poitiers, France

    L Roy

  16. Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia

    T Hughes

  17. Bristol–Myers Squibb, Wallingford, CT, USA

    R Ezzeddine & A M Countouriotis

  18. Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA

    H M Kantarjian

Authors
  1. A Hochhaus
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  2. M Baccarani
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  3. M Deininger
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  4. J F Apperley
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  5. J H Lipton
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  6. S L Goldberg
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  7. S Corm
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  8. N P Shah
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  9. F Cervantes
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  10. R T Silver
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  11. D Niederwieser
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  12. R M Stone
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  13. H Dombret
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  14. R A Larson
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  15. L Roy
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  16. T Hughes
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  17. M C Müller
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  18. R Ezzeddine
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  19. A M Countouriotis
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  20. H M Kantarjian
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Corresponding author

Correspondence to A Hochhaus.

Additional information

This trial (trial no. CA180-013) is registered at http://www.clinicaltrials.gov.

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Hochhaus, A., Baccarani, M., Deininger, M. et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 22, 1200–1206 (2008). https://doi.org/10.1038/leu.2008.84

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  • DOI: https://doi.org/10.1038/leu.2008.84

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