The Role of Imatinib in the Treatment of Chronic Myelogenous Leukemia

Author： Dax Kurbegov Hagop M. Kantarjian Moshe Talpaz

ISSN： 1175-6357

Source： American Journal of Cancer, Vol.3, Iss.6, 2004-01, pp. : 337-348

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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.