Nilotinib Therapy in Patients with Chronic Myeloid Leukemia Who Have Failed Imatinib

Chronic myeloid leukemia (CML) results from a single translocation that produces the BCR–ABL fusion oncogene, which is detectable in virtually all patients. Imatinib mesylate has radically changed the outlook for newly diagnosed patients and represents the current standard of care for this disorder. While most patients do well well with imatinib upfront, a minority of patients do not. In addition, this therapy offers little benefit for patients with advanced-phase disease. Several mechanisms underlie imatinib failure, point mutations within the Abelson tyrosine (ABL) kinase domain being the most significant of these. The development of novel agents designed to overcome imatinib resistance led to the creation of the high-affinity BCR-ABL inhibitor nilotinib. The purpose of this article is to summarize the pre-clinical and clinical data on nilotinib in patients with CML who have failed prior therapy with imatinib or dasatinib.