Dose Optimization of Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia.

Abstract

With the advent of newer treatments such as new molecular targeted agents and immunotherapies, the model that selects therapeutic doses on the basis of the maximum tolerated dose is no longer relevant. The emergence of tyrosine kinase inhibitor (TKI) therapy has changed the treatment prospects for chronic myeloid leukemia (CML) and prolonged the long-term survival of CML patients. However, long-term exposure to TKIs is accompanied by adverse events, which may lead to disease progression and even death. It can also increase economic pressure on patients and affect their health-related quality of life. In general, dose reduction is feasible and safe for most patients and can reduce the incidence of adverse events while ensuring efficacy, reduce the financial burden on patients and society, improve the quality of life of patients, and also as a prelude to an attempt at treatment-free remission (TFR). This review will classify the dose optimization of all approved TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, asciminib, radotinib) at different stages of treatment based on clinical trials and real-life studies, including dose optimization prior to attempting TFR. In addition, we briefly describe the application of therapeutic drug monitoring in dose optimization and the potential benefits of dose optimization on health-related quality of life.