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Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer

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Summary

Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3.0 mg/kg) every 2 weeks until disease progression or irAEs occurred. Clinical data regarding the duration of nivolumab treatment, symptoms, laboratory abnormalities, pathological findings of liver parenchyma biopsy specimens, and management of nivolumab-related cholangitis were analyzed. Results Our analysis revealed that nivolumab-related cholangitis was characterized by (1) localized extrahepatic bile duct dilation without obstruction; (2) diffuse hypertrophy of the extrahepatic bile duct wall; (3) a dominant increase in the biliary tract enzymes alkaline phosphatase and gamma-glutamyl transpeptidase relative to the hepatic enzymes aspartate and alanine aminotransferase; (4) normal or reduced levels of the serum immunological markers antinuclear antibody, antimitochondrial antibody, smooth muscle antibody, and immunoglobulin G4; (5) the pathological finding of biliary tract cluster of differentiation 8-positive T cell infiltration from liver biopsy; and (6) a moderate to poor response to steroid therapy. Conclusions Nivolumab-related cholangitis is associated with distinct imaging and clinicopathological features that distinguish it from acute cholangitis of common etiologies and other immune-related cholangitis. Further studies are warranted to establish the optimal management of patients with this irAE.

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Acknowledgements

We wish to thank to our colleagues in the Departments of Medical Oncology, Gastroenterology and Hepatology, and Pathology at Kindai University Faculty of Medicine (Osaka, Japan).

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Authors and Affiliations

  1. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Hisato Kawakami, Junko Tanizaki, Kaoru Tanaka, Koji Haratani, Hidetoshi Hayashi, Masayuki Takeda & Kazuhiko Nakagawa

  2. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Ken Kamata, Mamoru Takenaka & Masatoshi Kudo

  3. Department of Pathology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Masatomo Kimura, Takaaki Chikugo & Akihiko Ito

  4. Hospital Pathology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Takao Sato

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  1. Hisato Kawakami
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Correspondence to Hisato Kawakami.

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Conflict of interest

Hisato Kawakami declares that he has no conflict of interest. Junko Tanizaki declares that she has no conflict of interest. Kaoru Tanaka declares that he has no conflict of interest. Koji Haratani declares that he has no conflict of interest. Hidetoshi Hayashi declares that he has no conflict of interest. Masayuki Takeda declares that he has no conflict of interest. Ken Kamata declares that he has no conflict of interest. Mamoru Takenaka declares that he has no conflict of interest. Masatomo Kimura declares that he has no conflict of interest. Takaaki Chikugo declares that he has no conflict of interest. Takao Sato declares that he has no conflict of interest. Masatoshi Kudo declares that he has no conflict of interest. Akihiko Ito declares that he has no conflict of interest. Kazuhiko Nakagawa declares that he has no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Kawakami, H., Tanizaki, J., Tanaka, K. et al. Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer. Invest New Drugs 35, 529–536 (2017). https://doi.org/10.1007/s10637-017-0453-0

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