Case Report

*Author for correspondence: Tel.: +1 734 936 8596; Fax: +1 734 936 7392;

https://orcid.org/0000-0001-7741-1973

Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA

Search for more papers by this author

Bryan J Schneider

Division of Hematology & Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA

Search for more papers by this author

Lindsay M Brackett

Division of Hematology & Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA

Search for more papers by this author

Andrew W Tai

Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA

Search for more papers by this author

Published Online:2 Dec 2019https://doi.org/10.2217/imt-2019-0121

View article

Abstract

Immune checkpoint inhibitor therapy has become a cornerstone in the management of many oncologic diseases. Although it is well tolerated in most patients, a wide spectrum of adverse events has been described as a result of immune system alteration. We present a case of a woman with metastatic bronchogenic adenocarcinoma who was initially thought to have immune-mediated hepatitis, but eventually discovered to have a rarely described immune-mediated cholangiopathy. Her cholangiopathy appeared to stabilize following ursodeoxycholic acid and tocilizumab after several lines of guideline-directed therapy. Awareness of this unique toxicity following immune checkpoint inhibitor, and potential treatment options may help clinicians manage this rare but serious complication.

Keywords:

References

1. Corrales L, Scilla K, Caglevic C, Miller K, Oliveira J, Rolfo C. Immunotherapy in lung cancer: a new age in cancer treatment. Adv. Exp. Med. Biol. 995, 65–95 (2018).
MedlineGoogle Scholar
2. Naidoo J, Page DB, Li BT et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann. Oncol. 27(7), 1362 (2016).
Medline CASGoogle Scholar
3. Zarrabi K, Wu S. Risk of liver toxicity with nivolumab immunotherapy in cancer patients. Oncology 94(5), 259–273 (2018).
Medline CASGoogle Scholar
4. Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J. Clin. Oncol. 30(21), 2691–2697 (2012).
Medline CASGoogle Scholar
5. Kim KW, Ramaiya NH, Krajewski KM et al. Ipilimumab associated hepatitis: imaging and clinicopathologic findings. Invest. New Drugs 31(4), 1071–1077 (2013).
Medline CASGoogle Scholar
6. Johncilla M, Misdraji J, Pratt DS et al. Ipilimumab-associated hepatitis: clinicopathologic characterization in a series of 11 cases. Am. J. Surg. Pathol. 39(8), 1075–1084 (2015).
MedlineGoogle Scholar
7. Brahmer JR, Lacchetti C, Schneider BJ et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol. 36(17), 1714–1768 (2018).
Medline CASGoogle Scholar
8. Huffman BM, Kottschade LA, Kamath PS, Markovic SN. Hepatotoxicity after immune checkpoint inhibitor therapy in melanoma: natural progression and management. Am. J. Clin. Oncol. 41(8), 760–765 (2018).
Medline CASGoogle Scholar
9. Chmiel KD, Suan D, Liddle C et al. Resolution of severe ipilimumab-induced hepatitis after antithymocyte globulin therapy. J. Clin. Oncol. 29(9), e237–e240 (2011).
Medline CASGoogle Scholar
10. Stroud CR, Hegde A, Cherry C et al. Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade. J. Oncol. Pharm. Pract. 25(3), 551–557 (2019).
Medline CASGoogle Scholar
11. Doherty GJ, Duckworth AM, Davies SE et al. Severe steroid-resistant anti-PD1 T-cell checkpoint inhibitor-induced hepatotoxicity driven by biliary injury. ESMO Open 2(4), e000268 (2017).
MedlineGoogle Scholar
12. 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(4), 529–536 (2017).
Medline CASGoogle Scholar
13. Kashima J, Okuma Y, Shimizuguchi R, Chiba K. Bile duct obstruction in a patient treated with nivolumab as second-line chemotherapy for advanced non-small-cell lung cancer: a case report. Cancer Immunol. Immunother. 67(1), 61–65 (2018).
MedlineGoogle Scholar
14. Hamoir C, de Vos M, Clinckart F, Nicaise G, Komuta M, Lanthier N. Hepatobiliary and pancreatic: nivolumab-related cholangiopathy. J. Gastroenterol. Hepatol. 33(10), 1695 (2018).
Medline CASGoogle Scholar
15. Noda-Narita S, Mizuno S, Noguchi S et al. Development of mild drug-induced sclerosing cholangitis after discontinuation of nivolumab. Eur. J. Cancer 107, 93–96 (2019).
MedlineGoogle Scholar
16. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 127(26), 3321–3330 (2016).
Medline CASGoogle Scholar

Vol. 11, No. 18

Metrics

Downloaded 249 times

History

Received 19 July 2019

Accepted 5 November 2019

Published online 2 December 2019

Published in print December 2019

Information

Keywords

Author contributions

CA Reddy contributed in the design, preparation and review of the mansucript. BJ Schneider and AW Tai contributed in conceptualizing, designing and in the critical review of the manuscript. LM Brackett contributed in the critical review.

Informed consent disclosure

The authors state that they have obtained verbal informed consent from the patient for the inclusion of her medical and treatment history within this case report.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. The authors state that tocilizumab was given to the patient as part of clinical care when all standard-of-care options had failed. Institutional review board approval was not required for this.

PDF download

Nivolumab-induced large-duct cholangiopathy treated with ursodeoxycholic acid and tocilizumab

Abstract

References