Considerations on the dose and schedule of tyrosine kinase inhibitors for chronic myeloid leukemia: does dose matter?

Abstract: Tyrosine kinase inhibitors (TKIs) are the mainstay of treatment for patients with chronic myeloid leukemia. The standard dose has been established for each drug according to the indication for the various stages of the disease and whether as initial therapy or after failure of previous therapies. The recommended doses are fixed for all patients and dose adjustments are mostly recommended for management of adverse events. The standard doses have been derived largely from phase 1 studies, but as we discuss in this review, the current model may not be optimal for this purpose for drugs such as TKIs that are meant to be used for extended periods of time. Subsequent studies have led to changes in the initial recommendations for some drugs. In others, experience and real-world data have led to the use of TKIs using doses and adjustments that may be different than what clinical trials have recommended. In other scenarios, available data suggest that the current standard dose may need to be revisited. It may also be time to reconsider the standard approach of starting therapy with the standard dose and adjusting merely based on adverse events. We propose a flexible model that perhaps reflects more accurately what is being done frequently in the clinic.