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Chronic Myeloproliferative Neoplasias

Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: response dynamics and predictive value

Leukemia volume 23, pages 1628–1633 (2009)Cite this article

Abstract

Dasatinib is a highly potent BCR–ABL inhibitor that has shown durable efficacy in patients with chronic phase (CP) chronic myeloid leukemia (CML) after resistance, suboptimal response, or intolerance to prior imatinib. In patients with CML, BCR–ABL transcript measurement is the most sensitive method for assessing minimal residual disease. Here, molecular responses were analyzed in 1067 patients with CML-CP treated with dasatinib during phase II/III trials. After 3, 6, 12, and 24 months of follow-up, a major molecular response (MMR) was achieved by 12, 22, 35, and 40% of patients, respectively. The 24-month MMR rate was 34% in patients with resistance or suboptimal response to imatinib (n=829) and 63% in imatinib-intolerant patients (n=238). Among patients who had achieved a complete cytogenetic response (CCyR), 72% also achieved MMR. Responses with dasatinib 100 mg once daily were similar to other doses. In landmark analyses, 24-month progression-free survival was higher in patients who had achieved MMR or CCyR at 12 months than in those without MMR or CCyR at 12 months. MMR at 12 months was associated with a longer duration of CCyR. Overall, this analysis shows that dasatinib treatment results in high MMR rates in patients with CML-CP after imatinib failure.

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Acknowledgements

We thank the many investigators and centers who participated in the START-C, START-R, and CA180-034 studies. Funding for clinical trials, statistical analysis, and professional medical writing assistance was provided by Bristol-Myers Squibb. AH was supported by the German José-Carreras Foundation (DJCLS H 03/01).

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Authors and Affiliations

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

    A Hochhaus, M C Müller & B Hanfstein

  2. Department Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

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

    J Radich

  4. Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia

    S Branford & T P Hughes

  5. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H M Kantarjian

  6. Service d’Hématologie et d’Oncologie, Hôpital André Mignot, Université de Versailles et CIC9504, France

    P Rousselot

  7. St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea

    D-W Kim

  8. Department of Hematology/Medical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada

    J H Lipton

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

    E Bleickardt & A Lambert

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  1. A Hochhaus
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  2. M C Müller
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Correspondence to A Hochhaus.

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Hochhaus, A., Müller, M., Radich, J. et al. Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: response dynamics and predictive value. Leukemia 23, 1628–1633 (2009). https://doi.org/10.1038/leu.2009.156

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  • DOI: https://doi.org/10.1038/leu.2009.156

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