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The Role of Imatinib in the Treatment of Chronic Myelogenous Leukemia

  • Current Opinion
  • Published:
American Journal of Cancer

Abstract

The Philadelphia chromosome and resultant Bcr-Abl fusion protein define most cases of chronic myelogenous leukemia (CML). The characterization of this protein and its integral role in the pathogenesis of leukemia has led to the development of specific inhibitors of Bcr-Abl which possess potent anti-tumor activity both in vitro and in vivo.

Imatinib, the only widely available Bcr-Abl inhibitor, represents the paradigm for rational drug development in the treatment of malignancies. It is highly effective in the treatment of chronic phase CML disease, producing a 95% complete hematologic response rate in interferon (IFN)-resistant patients. In contrast to IFN-based therapy, the majority of patients on imatinib will achieve a major cytogenetic response, suggesting a potential survival benefit. Imatinib also has a significantly more favorable toxicity profile than IFN or transplant-based strategies. Importantly, progression to the accelerated or blastic phases of the disease is rare in patients responding to imatinib.

On the basis of these findings, the majority of patients with chronic phase CML should be considered for a trial of therapy with imatinib, either in the clinic or in the context of a clinical trial. Failure to achieve a complete hematologic response within 3 months or a cytogenetic response within 6 months should lead to consideration of allogeneic transplantation, IFN therapy or participation in available clinical trials. While a substantial proportion of patients with accelerated or blastic phase disease will have a response to imatinib, these responses are transient with eventual resistance as the rule. Therefore, single-agent treatment with imatinib in this setting is not recommended unless it is used as a bridge to more definitive therapy such as transplantation.

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Fig. 1
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Notes

  1. The recommendations elaborated in this manuscript contain a range of approaches for the treatment of patients with CML. The discussion focuses on the emerging role of imatinib in this setting. As such, it is beyond the scope of this article to comprehensively evaluate all potential therapeutic options, both conventional and experimental, which may have relevance to an individual patient. Ultimately, therapeutic decisions must be made jointly by the physician and patient in the context of rapidly emerging data and the specific issues and concerns of the patient.

  2. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgment

Dr Talpaz and Dr Kantarjian have been supported through clinical grants from the following companies: Novartis, Roche, and Schering-Plough Pharmaceuticals. The authors wish to thank Interlink Healthcare Communications, Inc., for the graphic design of figure 1, figure 2, and figure 3.

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  1. M.D. Anderson Cancer Center, The University of Texas, Houston, Texas, USA

    Dax Kurbegov, Hagop M. Kantarjian &  Moshe Talpaz

  2. Department of Experimental Therapeutics, MD Anderson Cancer Center, Box 422, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Moshe Talpaz

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  1. Dax Kurbegov
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Correspondence to Moshe Talpaz.

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Kurbegov, D., Kantarjian, H.M. & Talpaz, M. The Role of Imatinib in the Treatment of Chronic Myelogenous Leukemia. Am J Cancer 3, 337–348 (2004). https://doi.org/10.2165/00024669-200403060-00002

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