Long-term safety review of tyrosine kinase inhibitors in chronic myeloid leukemia - What to look for when treatment-free remission is not an option

Abstract

The development of BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myeloid leukemia (CML). Although there are some common class-wide side effects, differences in safety profiles between TKIs allow physicians and patients to personalize treatment plans. Treatment selection depends on several factors, such as age, disease risk, comorbidities, and concomitant medications. In second- and later-line settings, response to previous TKIs and mutation analyses should also be used to guide TKI selection. Several strategies can be used to manage adverse events (AEs) that emerge during treatment, e.g., dose reductions/interruptions, monitoring, treatment of AEs, lifestyle modifications, prophylactic therapy, and other supportive care strategies. This review summarizes the safety profiles of the currently approved TKIs and how they impact treatment selection in the first- and later-line settings of CML, particularly regarding patient comorbidities and concomitant medications. Additionally, strategies to manage AEs of special interest with TKIs are reviewed.

Keywords: Adverse events; Chronic myeloid leukemia; Long-term; Safety; Tyrosine kinase inhibitors.