Nilotinib and dasatinib – current place in the therapy of chronic myeloid leukemia

Abstract

Tyrosine kinase inhibitors (TKI) have revolutionized the practise of treatment of chronic myeloid leukemia. The emergence of resistance to imatinib – first TKI – has led to the development of second-generation TKI's (2GTKI). Nilotinib and dasatinib are 2GTKI's routinely used in the tretament of CML patients intolerant or resistant to imatinib since couple of years. The approval of nilotinib and dasatinib in newly diagnosed chronic-phase CML patients was granted based on the results of studies comparing 2GTKI's with imatinib used in the first-line setting. More patients treated up-front with nilotinib or dasatinib reach early molecular response, and deep molecular response (DMR), which is achieved quicker than under imatinib therapy. The achievement of EMR increases the chance for major molecular response and may prolong progression-free and overall survival. DMR is one of the key eligibility criteria to TKI – discontinuation trials. Considering the current goal of CML therapy, reducing the time of exposure to adverse drug reactions and health economic aspects, the early achievement of DMR with the use of 2GTKI and subsequently discontinuation of therapy seems to be a reasonable and safe treatment strategy for substantial proportion of patients.