Tyrosine kinase inhibitors (TKIs) have demonstrated long-term survival benefits for patients with chronic myeloid leukemia (CML). But the risks associated with use of these agents, notably long-term TKI-associated vascular adverse events (VAEs), are concerning.
Therefore, a team of researchers conducted a retrospective cohort study to determine the incidence of VAEs in patients with CML treated with imatinib, nilotinib, or dasatinib. The researchers pulled data from the Taiwan Cancer Registry Database and the National Health Insurance Research Database, including a total of 1111 patients with CML. Their findings were published in The Oncologist.
Only patients whose first-line treatment was TKIs were included, and unlike previous studies, this study also excluded patients with a history of VAEs to reduce the potential for misclassification of recurrent VAEs as study endpoints.
These findings suggest that patients treated with nilotinib or dasatinib are at increased risk of VAEs; however, the increase was statistically significant only in those treated with nilotinib. Incidence of VAEs in these patients was highest in the first year of treatment then declined.
Older age and a history of cerebrovascular disease also may increase the risk of VAEs with second-generation TKIs. Thus, patients with CML who are older or have a history of cerebrovascular disease should be closely monitored, particularly in the first year of TKI therapy, the researchers explained, noting that caution is especially important when nilotinib or dasatinib is the initial treatment.
Compared with the patients who did not experience VAEs, many of those who did were more likely to have comorbidities such as dyslipidemia, diabetes, hypertension, congestive heart failure, cardiovascular disease, and renal failure.
Study limitations included a lack of information on variables such as family history and social history. The researchers pointed out that CML might also contribute to VAEs, and it would be difficult to conduct a comparison between people with CML who are not treated with TKIs and the general population, as TKIs are generally considered the gold standard and introducing CML patients who did not receive this type of treatment may introduce tremendous selection bias. The follow-up period for patients treated with dasatinib and nilotinib was shorter than in some previous studies, although most VAEs occur within 1 to 3 years after TKI initiation.
Chen MT, Huang ST, Lin CW, et al. Tyrosine kinase inhibitors and vascular adverse events in patients with chronic myeloid leukemia: a population-based propensity score-matched cohort study. Oncologist. August 21, 2021. doi:10.1002/onco.13944