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

Mei-Tsen Chen; Shih-Tsung Huang; Chih-Wan Lin; Bor-Sheng Ko; Wen-Jone Chen; Huai-Hsuan Huang; Fei-Yuan Hsiao

doi:10.1002/onco.13944

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

Oncologist. 2021 Nov;26(11):974-982. doi: 10.1002/onco.13944. Epub 2021 Sep 12.

Authors

Mei-Tsen Chen¹, Shih-Tsung Huang¹, Chih-Wan Lin¹, Bor-Sheng Ko^{2

3}, Wen-Jone Chen⁴, Huai-Hsuan Huang², Fei-Yuan Hsiao^{1

5

6}

Affiliations

¹ Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan.
² Division of Hematology, National Taiwan University Hospital, Taipei, Taiwan.
³ Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
⁴ Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁵ School of Pharmacy, National Taiwan University, Taipei, Taiwan.
⁶ Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.

Abstract

Background: Tyrosine kinase inhibitors (TKIs) have shown long-term survival benefits in patients with chronic myeloid leukemia (CML). 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 patients with CML treated with different TKIs (imatinib, nilotinib, and dasatinib) as well as potential risk factors.

Materials and methods: We conducted a retrospective cohort study using the Taiwan Cancer Registry Database and National Health Insurance Research Database. 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 patients with CML were included in our study. We found that the risk of VAEs in nilotinib users was significantly higher than that in imatinib users, with an HR of 3.13 (95% confidence interval (CI), 1.30-7.51), whereas 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 patients with CML in Taiwan.

Implications for practice: This study found that patients with chronic myeloid leukemia (CML) treated with nilotinib and dasatinib may be exposed to a higher risk of developing vascular adverse events (VAEs) compared with those treated with imatinib. Thus, this study suggests that patients with CML 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 tyrosine kinase inhibitors.

Keywords: Chronic myeloid leukemia; Tyrosine kinase inhibitors; Vascular adverse events.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cohort Studies
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
Propensity Score
Protein Kinase Inhibitors / adverse effects
Retrospective Studies

Substances

Protein Kinase Inhibitors