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Assessment of estimated glomerular filtration rate in patients with chronic myeloid leukemia following discontinuation of tyrosine kinase inhibitors

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Abstract

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically improved survival outcomes in patients with chronic phase chronic myeloid leukemia (CML-CP) and are associated with a manageable safety profile. However, long-term TKI administration can lead to cardiovascular or renal adverse events. One goal in discontinuation of TKIs was reduction of adverse events, but it is unclear whether chronic toxicities are ameliorated as a result. In this study, we evaluated changes in estimated glomerular filtration rate (eGFR) in patients with CML-CP before and after TKI discontinuation. Long-term TKI treatment appears to induce renal toxicity, as eGFR at the time of TKI discontinuation correlated with the duration of TKI treatment (r = − 0.478, p = 0.005). Patients who received imatinib as first-line treatment exhibited lower eGFR levels than those treated with dasatinib or nilotinib, which may be correlated with long-term treatment (p = 0.027). After TKI discontinuation, no significant increases in eGFR were seen either in patients with treatment-free remission (66.8–71.2 ml/min/1.73 m2) or molecular relapse (64.8–68.7 ml/min/1.73 m2, p = 0.666). These data indicate that TKI-induced renal toxicities are associated with long-term TKI treatment, and may be irreversible even following treatment discontinuation.

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Acknowledgements

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Funding

This work was supported by research grants from JSPS KAKENHI (19K17860, HU) and JSPS KAKENHI (17K09908, SK).

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Authors and Affiliations

  1. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Sho Okamoto, Hiroshi Ureshino & Shinya Kimura

  2. Department of Internal Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan

    Sho Okamoto

  3. Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan

    Hiroshi Ureshino & Shinya Kimura

  4. Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Atsushi Kawaguchi

  5. Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Motoaki Miyazono & Yuji Ikeda

Authors
  1. Sho Okamoto
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  2. Hiroshi Ureshino
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  3. Atsushi Kawaguchi
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  4. Motoaki Miyazono
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  5. Yuji Ikeda
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  6. Shinya Kimura
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Corresponding author

Correspondence to Hiroshi Ureshino.

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Conflict of interest

SK has received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals, and research funding from Bristol-Myers Squibb, Novartis, Pfizer, Otsuka Pharmaceuticals, and Ohara Pharmaceuticals. The other authors declare no potential conflicts of interest.

Ethical approval

This study was approved by the Institutional Review Board of Saga University. All procedures involving human participants were performed in accordance with the ethical standards of institutional and/or national research committees, and the Declaration of Helsinki.

Informed consent

Informed consent was waived because of the retrospective design of the data collection. Information of the research, including the aims of use of specimens and the opportunity to opt out from the research, was made public. No patients objected to this study.

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Okamoto, S., Ureshino, H., Kawaguchi, A. et al. Assessment of estimated glomerular filtration rate in patients with chronic myeloid leukemia following discontinuation of tyrosine kinase inhibitors. Int J Hematol 112, 41–45 (2020). https://doi.org/10.1007/s12185-020-02880-3

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  • DOI: https://doi.org/10.1007/s12185-020-02880-3

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