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Evolving treatment strategies for patients newly diagnosed with chronic myeloid leukemia: the role of second-generation BCR–ABL inhibitors as first-line therapy

Leukemia volume 26, pages 214–224 (2012)Cite this article

Abstract

In patients with chronic myeloid leukemia (CML), disease in the initial chronic phase (CP) and subsequent progression are driven by the oncogenic activity of the BCR–ABL fusion kinase. Imatinib, a tyrosine kinase inhibitor of BCR–ABL, has been the mainstay of first-line therapy for CML for 10 years. Although patients with CML–CP respond well to imatinib, those who have delayed reductions in leukemic burden during imatinib therapy, such as not achieving a complete cytogenetic response (CCyR) by 12 months, have an increased risk of disease progression. It has been recognized, with 8 years of observation, that patients who achieve an early major molecular response (MMR) on imatinib have a very low probability of disease progression. Recent randomized phase 3 trials have shown that first-line treatment with dasatinib or nilotinib—more potent BCR–ABL inhibitors—results in significantly higher rates and more rapid achievement of CCyR and MMR in comparison with standard-dose imatinib. These trials suggest that CML treatment can be improved with more potent BCR–ABL inhibition during initial therapy, but further follow-up is needed to confirm that the improved response rates with dasatinib and nilotinib are maintained long term.

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Acknowledgements

The authors have contributed significantly to this paper, take full responsibility for the content of this article and confirm that it reflects their viewpoint and medical expertise. StemScientific, funded by Bristol-Myers Squibb, provided writing and editing support. Bristol-Myers Squibb did not in any way influence the content of the paper nor did the authors receive financial compensation for authoring the article. This study was supported by NIH Grants HL082978-01 (MD), CA04963920A2 (MD), 1R01CA129611 (PJS), Leukemia and Lymphoma Society grant 7036-01 (MD). MD is a Scholar in Clinical Research of the Leukemia and Lymphoma Society.

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  1. Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    P J Shami & M Deininger

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M Deininger is a paid consultant for Novartis, Bristol-Myers Squibb and ARIAD. PJ Shami has participated in Advisory Boards and Speaker Bureau for Novartis.

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Shami, P., Deininger, M. Evolving treatment strategies for patients newly diagnosed with chronic myeloid leukemia: the role of second-generation BCR–ABL inhibitors as first-line therapy. Leukemia 26, 214–224 (2012). https://doi.org/10.1038/leu.2011.217

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