Tyrosine Kinase Inhibitors and Vascular Adverse Events in Patients with Chronic Myeloid Leukemia: A Population-Based, Propensity Score-Matched Cohort Study

Abstract

Background. Tyrosine kinase inhibitors (TKIs) have shown long-term survival benefits in chronic myeloid leukemia (CML) patients. Nevertheless, significant concern has been raised regarding long-term TKI-associated vascular adverse events (VAEs). The objective of this retrospective cohort study was to investigate the incidence of VAEs in Taiwanese CML patients treated with different TKIs (imatinib, nilotinib, and dasatinib) as well as potential risk factors. Methods. We conducted a retrospective cohort study using the Taiwan Cancer Registry Database (TCRD) and National Health Insurance Research Database (NHIRD). Adult patients diagnosed with CML from 2008 to 2016 were identified and categorized into three groups according to their first-line TKI treatment (imatinib, nilotinib, and dasatinib). Propensity score matching was performed to control for potential confounders. Cox regressions were used to estimate the hazard ratio (HR) of VAEs in different TKI groups. Results. In total, 1,111 CML patients were included in our study. We found that the risk of VAEs in nilotinib users was significantly higher than that in imatinib users, with a hazard ratio (HR) of 3.13 (95% confidence interval (CI) 1.30-7.51), while dasatinib users also showed a nonsignificant trend for developing VAEs, with an HR of 1.71 (95% CI 0.71-4.26). In multivariable logistic regression analysis, only nilotinib usage, older age and history of cerebrovascular diseases were identified as significant risk factors. The annual incidence rate of VAEs was highest within the first year after the initiation of TKIs. Conclusion. These findings can support clinicians in making treatment decisions and monitoring VAEs in CML patients in Taiwan. The Oncologist 2021;9999:• • Implications for Practice: Our study found that CML patients treated with nilotinib and dasatinib may exposed to higher risk of developing vascular adverse events compared to those who treated with imatinib. Thus, we suggest that CML patients who are older or have a history of cerebrovascular diseases should be under close monitoring of VAEs, particularly within the first year after the initiation of TKIs.

Nilotinib related acute myocardial infarction with nonobstructive coronary arteries: a case report and literature review

“…However, in recent years, vasculotoxicity or vascular adverse events (VAE) (including peripheral arteries and coronary artery) have become a concern in patients receiving such treatment [ 9 ]. Although not fully characterized, based on three retrospective studies [ 9 – 11 ], patients who developed TKI-related VAE commonly had their first VAE onset within the first year. For this patient, he started the medication (nilotinib) since Dec. 2019, and had AMI 9 months (Aug. 2020) afterward.…”

“…Compared to the first generation BCR-ABL TKI (imatinib), the risk of VAE with nilotinib (second generation BCR-ABL TKI) was over threefold higher [ 11 ]. In one pooled analysis of three prospective clinical studies, during a quite long follow-up of 77 months in 108 patients who were treated with nilotinib, the incidence of angina/MI was 6% (7/108) [ 10 ].…”

Dose modification dynamics of ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) from the PACE and OPTIC trials

“…In the absence of head-to-head trials, propensity score matching enables estimation and comparison of treatment effects and dosing strategies [ 36 ]. For example, propensity score–matched analyses have been used to compare efficacy and safety outcomes in patients with CP-CML receiving front-line imatinib, nilotinib, or dasatinib [ 37 , 38 ]. Using this approach, we were able to perform comparisons of TE-AOE rates in PACE and OPTIC trial populations.…”

Multidisciplinary management in chronic myeloid leukemia improves cardiovascular risk measured by SCORE

“…However, according to previous studies, it seems that nilotinib is more associated with the development or worsening of arterial hypertension ( Roa-Chamorro et al, 2021 ), as well as coronary disease together with dasatinib ( Barber et al, 2017 ). Nilotinib is especially associated with stroke ( Chen et al, 2021 ), as well as peripheral arterial disease together with dasatinib ( Chen et al, 2021 ). However, treatment with ponatinib has been the most associated with hypertension (17% vs. 10%) for all new-generation TKI in a pooled analysis of hypertension incidence ( Mulas et al, 2021 ) and thrombotic risk (10% patients developed cerebrovascular or vaso-occlusive disease) ( Jain et al, 2015 ).…”