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ASCO Educational Book; 2009
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Imatinib As Frontline Therapy for Patients with Newly Diagnosed Chronic-phase Chronic Myeloid Leukemia

Dale Bixby, MD, PhD, and Moshe Talpaz, MD

From the Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

Address reprint requests to Moshe Talpaz, MD, 1500 East Medical Center Dr., 4302 CCC/SPC 5936, Ann Arbor, MI 48109-5936; e-mail: mtalpaz{at}umich.edu

Overview: Chronic myeloid leukemia (CML) is a relatively rare entity, with an annual incidence of only 4,800 cases in the United States.1 However, improvements in the last decade in the understanding of the molecular pathogenesis of the disease, coupled with exceptional advances seen with molecular targeting of the initiating tyrosine kinase, have brought this disease to center stage in the oncologic arena. Indeed, imatinib, which inhibits the Bcr-Abl tyrosine kinase thought to initiate and propagate CML, has become the therapeutic standard for patients with newly diagnosed chronic-phase CML. Yet, a substantial fraction of these patients will have an inferior response to imatinib, either failing to respond to primary therapy or demonstrating progression after the initial response is seen.2-3 Identifying these patients early is critical in the management of CML; efforts to distinguish patients with a high risk of imatinib resistance at the time of diagnosis are ongoing. Recently, a number of therapeutic trials utilizing either alternative imatinib schedules or newer tyrosine kinase inhibitors have attempted to improve on the therapeutic results of imatinib. This review will summarize the understanding of the achievements and limitations of imatinib in primary CML therapy, followed by a discussion on the alternatives for initial treatment of newly diagnosed patients. Given the remarkable outlook for the majority of newly diagnosed patients treated with imatinib coupled with the increasing number of new therapeutic options available, it is exceedingly important that optimal trials are conducted to identify the most advantageous treatment regimen in this patient population.