Arterio-occlusive events among patients with chronic myeloid leukemia on tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKIs) are standard therapy for patients with chronic myeloid leukemia. Each of these drugs has a speci fi c pro fi le of tyrosine kinases that they inhibit and, although all are clinically effective, they each have unique toxicity pro fi les. With the introduction of ponatinib, arterio-occlusive events were fi rst noted and later found to occur with all TKIs to various extents. The recognition of this "class effect" was delayed considering ponatinib was introduced 10 years after the introduction of imatinib. The reasons for the delay in identi fi cation of this class effect are likely multifaceted. Importantly, there is an inconsistency in adverse event reporting criteria among the major clinical trials of the various TKIs, likely resulting in mixed reporting of arterio-occlusive events. Reporting events based on a frequency threshold, lack of suf fi cient follow-up, attempts at causality attribution, and the primary focus on molecular response may all have played an additional role. Considering the increasing rate of arterio-occlusive events over time, the termination of many trials after only 5 years prevents full assessment of the impact of these events. A comprehensive evaluation of TKI adverse effects using uniform Medical Dictionary for Regulatory Activities terms and comprehensive adjudication of these events may be helpful in better assessing the real risk for patients with each TKI. Future clinical trials should use a uniform and comprehensive approach to reporting adverse events without attempting to assign causality to the study drug.