Nilotinib for the treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia: review of the latest clinical evidence

Author(s): Massimo Breccia, Giuliana Alimena

Nilotinib is a second-generation tyrosine kinase inhibitor 30-fold more potent than imatinib, with high affinity and selectivity on breakpoint cluster region/V-abl Abelson murine leukemia viral oncogene homolog 1, and also active against a wide range of mutant clones. Phase II trials of nilotinib showed high activity in imatinib-resistant or -intolerant chronic myeloid leukemia patients. Recently, the results of nilotinib as frontline treatment showed high efficacy and superiority as compared with imatinib. Two independent Phase II trials (Italian Group for Adult Hematologic Diseases [GIMEMA] and MD Anderson Cancer Center [MDACC] experiences), testing nilotinib as single agent at standard dose in newly diagnosed patients, showed high rate of cytogenetic and molecular responses with few cases of disease progression. The Phase III randomized Evaluating Nilotinib Efficacy and Safety in Clinical Trials – newly diagnosed patients (ENESTnd) study results demonstrated higher cytogenetic and molecular responses after 24 months (overall major molecular response rate, 62% for nilotinib 300 mg twice daily, 59% for nilotinib 400 mg twice daily compared with 37% for imatinib; overall best complete cytogenetic response rate, 87% for nilotinib 300 mg twice daily, 85% for nilotinib 400 mg twice daily compared with 77% with imatinib), lower rate of progression compared with imatinib (0.7% for nilotinib 300 mg twice daily, 1.1% for nilotinib 400 mg twice daily and 4.2% with imatinib). This article provides substantial evidence on the efficacy and relative tolerability of nilotinib in the management of early chronic phase chronic myeloid leukemia patients.