Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National Population-Based Cohort Study

Cih En Huang, Kuan Der Lee, Jung Jung Chang, Huey En Tzeng, Shih Hao Huang, Lennex Hsueh Lin Yu*, Min Chi Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear.

METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models.

RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively.

CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.

Original languageEnglish
Pages (from-to)E81-E89
JournalOncologist
Volume29
Issue number1
DOIs
StatePublished - 05 01 2024

Bibliographical note

© The Author(s) 2023. Published by Oxford University Press.

Keywords

  • cardiovascular diseases
  • chronic myeloid leukemia
  • diabetes
  • hyperlipidemia
  • nilotinib
  • Dasatinib
  • Diabetes Mellitus/chemically induced
  • Humans
  • Cardiovascular Diseases/chemically induced
  • Metabolic Syndrome/chemically induced
  • Hypertension/chemically induced
  • Imatinib Mesylate
  • Protein Kinase Inhibitors/adverse effects
  • Pyrimidines/adverse effects
  • Hyperlipidemias/chemically induced
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications
  • Cohort Studies

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