Critical appraisal of nilotinib in frontline treatment of chronic myeloid leukemia

Abstract

David L DeRemer1,2, Katerina Katsanevas1,2, Celalettin Ustun31Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Augusta, GA, USA; 2Medical College of Georgia Health inc, Augusta, GA, USA; 3Department of Medicine, Section of Hematology/Oncology, University of Minnesota, Minneapolis, MN, USAAbstract: The development of imatinib has revolutionized the treatment of chronic myeloid leukemia. Follow-up analysis of IRIS trial participants continues to demonstrate durable responses for imatinib at 400 mg/day. However, 10%–15% of patients with chronic myeloid leukemia will become imatinib-resistant or intolerant of adverse events. Phase II studies have shown that most of these patients will respond to second-generation tyrosine kinase inhibitors, such as nilotinib, dasatinib, and bosutinib. Both nilotinib and dasatinib have recently demonstrated clinical efficacy as frontline therapy in Phase III studies. In the ENESTnd trial, nilotinib 600–800 mg/day produced significantly higher major molecular rates and complete cytogenetic response rates in comparison with imatinib at 12 months. Recently, 18-month follow-up analysis of this trial continues to demonstrate superiority for nilotinib. It is unknown whether this will ultimately translate into improved long-term outcomes, such as event-free survival or overall survival. Nilotinib continues to be generally well tolerated and tends to produce less Grade 3/4 toxicity in frontline therapy when compared with its use following imatinib failure. With three tyrosine kinase inhibitors for potential frontline therapy and an active drug discovery pipeline, treatment for chronic myeloid leukemia is still subject to change with time as clinical algorithms continue to evolve.Keywords: nilotinib, frontline therapy, chronic myeloid leukemia, adverse events