Treatment-, Patient-, and Disease-Related Factors and the Emergence of Adverse Events with Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia

Four breakpoint cluster region (BCR)-ABL1 tyrosine kinase inhibitors ( s) are currently available for the treatment of chronic myeloid leukemia (CML): imatinib, nilotinib, dasatinib, and bosutinib. Choosing the most appropriate requires clinicians to consider a host of patient-, disease-, and treatment-related factors, not the least of which include the safety profiles of the agents. therapy, with a focus on the underlying mechanisms believed to be responsible for a number of important adverse events associated with these agents and what implications they may have for treatment choice, particularly in the setting of first-line treatment. A literature search of the PubMed database was conducted to identify articles that described the molecular mechanisms of BCR-ABL1-mediated leukemic transformation, the efficacy and safety of imatinib, nilotinib, dasatinib, and bosutinib in patients with CML, the kinase-binding spectrum of each , and evidence suggesting a link between the -binding profile and adverse events. . Clinical studies suggest that imatinib, nilotinib, dasatinib, and bosutinib have differing safety profiles, which are in part attributable to the specificity and selectivity of each agent. Although much basic research must be conducted to further illuminate the mechanisms responsible for -related adverse events, on- and off-target effects are believed to be at least partly responsible for cardiovascular toxicity, myelosuppression, fluid retention, gastrointestinal toxicity, and dermatologic toxicity. Increased understanding of the factors that affect -associated adverse events and long-term safety data will enable a more informed approach to the selection of therapy best suited to the individual needs of patients with CML.