Nilotinib therapy in chronic myelogenous leukemia: the strength of high selectivity on BCR/ABL

Imatinib mesylate is currently the standard therapy for chronic myeloid leukemia (CML) patients. Despite the remarkable results achieved with imatinib, the emergence of resistance to this drug has become a significant problem. Several strategies have been developed to overcome imatinib resistance, including dose escalation of the drug, combination treatments or novel targeted agents. Nilotinib is a second-generation tyrosine kinase inhibitor 30-50 fold more potent than imatinib with high affinity and selectivity on BCR/ABL, active against a wide range of mutant clones, except T315I mutation. Phase II trials of nilotinib showed high activity in imatinib-resistant or intolerant CML patients; front-line treatment of chronic phase Ph+ CML demonstrated rapid and stable cytogenetic responses and increasing molecular responses. We here review the development of nilotinib and the efficacy data in phase II and front-line trials.