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When Imatinib Fails, What Else Is There?

From the Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, TX

Author's disclosure of potential conflicts of interest are found at the end of this article.

Address reprint requests to Jorge Cortes, MD, Professor of Medicine, Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030; e-mail: jcortes{at}mdanderson.org

Overview: Most patients with chronic myeloid leukemia (CML) treated with imatinib have a favorable outcome. For those in whom imatinib fails, second-generation tyrosine kinase inhibitors (dasatinib, nilotinib, and bosutinib) have demonstrated efficacy with a favorable toxicity profile. Although these agents are all tyrosine kinase inhibitors, they all have a different biochemical structure, spectrum, and mechanism of action. As patients receive sequential therapies, some have experienced failure with two tyrosine kinase inhibitors or more or have the multiresistant T315I. Therapy in these instances is mostly ineffective. Several new agents are being developed for these patients with promising results. The rapid development of therapies for all patients with CML is a model in cancer therapy that has resulted in a marked improvement in the outcome of patients with CML.