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Immunotherapy pp 151-157 | Cite as

Immune Checkpoint Inhibitors-Induced Colitis

  • Yun Tian
  • Hamzah Abu-Sbeih
  • Yinghong WangEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 995)

Abstract

Immune checkpoint inhibitors (ICIs) have shown significant benefit in cancer patients, but are associated with immune-related adverse events (irAEs), that can affect the gastrointestinal tract resulting in diarrhea and colitis. IrAEs range from mild self-limiting to severe life-threatening disease, which potentially limit the use of these medications. Diagnosis of ICI-induced colitis is based on clinical symptoms, physical examination, stool tests, endoscopic evaluation, and/or imaging. Current management strategy is mainly anti-diarrheal agents for mild symptoms, and immunosuppressants (e.g., corticosteroids, and infliximab or vedolizumab) for more severe cases.

Keywords

Immune checkpoint inhibitors Colitis Diarrhea Corticosteroids Infliximab Steroids Immunotherapy 

Notes

Disclosure

The authors declared no financial conflict of interest.

References

  1. 1.
    Marthey L, Mateus C, Mussini C, et al. Cancer immunotherapy with Anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis. 2016;10:395–401.CrossRefGoogle Scholar
  2. 2.
    Gupta A, De Felice KM, Loftus EV Jr, Khanna S. Systematic review: colitis associated with anti-CTLA-4 therapy. Aliment Pharmacol Ther. 2015;42:406–17.CrossRefGoogle Scholar
  3. 3.
    Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016;54:139–48.CrossRefGoogle Scholar
  4. 4.
    Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB. Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol. 2017;8:49.CrossRefGoogle Scholar
  5. 5.
    Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.CrossRefGoogle Scholar
  6. 6.
    Wang Y, Abu-Sbeih H, Mao E, Ali N, Ali FS, Qiao W, et al. Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson. J Immunother Cancer. 2018;6(1):37.CrossRefGoogle Scholar
  7. 7.
    Beck KE, Blansfield JA, Tran KQ, et al. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol. 2006;24:2283–9.CrossRefGoogle Scholar
  8. 8.
    Johnston RL, Lutzky J, Chodhry A, Barkin JS. Cytotoxic T-lymphocyte-associated antigen 4 antibody-induced colitis and its management with infliximab. Dig Dis Sci. 2009;54:2538–40.CrossRefGoogle Scholar
  9. 9.
    de Guillebon E, Roussille P, Frouin E, Tougeron D. Anti program death-1/anti program death-ligand 1 in digestive cancers. World J Gastrointest Oncol. 2015;7:95–101.CrossRefGoogle Scholar
  10. 10.
    Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–28.CrossRefGoogle Scholar
  11. 11.
    Howell M, Lee R, Bowyer S, Fusi A, Lorigan P. Optimal management of immune-related toxicities associated with checkpoint inhibitors in lung cancer. Lung Cancer. 2015;88:117–23.CrossRefGoogle Scholar
  12. 12.
    Ledezma B, Binder S, Hamid O. Atypical clinical response patterns to ipilimumab. Clin J Oncol Nurs. 2011;15:393–403.CrossRefGoogle Scholar
  13. 13.
    Common terminology criteria for adverse events (CTCAE) version 4.0. US Department of Health and Human Services.Google Scholar
  14. 14.
    Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30:2691–7.CrossRefGoogle Scholar
  15. 15.
    Weber J. Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist. 2007;12:864–72.CrossRefGoogle Scholar
  16. 16.
    Lord JD, Hackman RC, Moklebust A, et al. Refractory colitis following anti-CTLA4 antibody therapy: analysis of mucosal FOXP3+ T cells. Dig Dis Sci. 2010;55:1396–405.CrossRefGoogle Scholar
  17. 17.
    Pernot S, Ramtohul T, Taieb J. Checkpoint inhibitors and gastrointestinal immune-related adverse events. Curr Opin Oncol. 2016;28:264–8.CrossRefGoogle Scholar
  18. 18.
    Eggermont AM, Chiarion-Sileni V, Grob JJ. Correction to Lancet Oncol 2015; 16: 522-30. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16:e262.CrossRefGoogle Scholar
  19. 19.
    McCutcheon JL, McClain CM, Puzanov I, Smith TA. Infectious colitis associated with ipilimumab therapy. Gastroenterol Res. 2014;7:28–31.Google Scholar
  20. 20.
    Berman D, Parker SM, Siegel J, et al. Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma. Cancer Immun. 2010;10:11.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Abu-Sbeih H, Ali FS, Luo W, Qiao W, Raju GS, Wang Y. Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis. J Immunother Cancer. 2018;6(1):95.CrossRefGoogle Scholar
  22. 22.
    Wang Y, Abu-Sbeih H, Mao E, Ali N, Qiao W, Trinh VA, et al. Endoscopic and histologic features of immune checkpoint inhibitor-related colitis. Inflamm Bowel Dis. 2018;24(8):1695–705.CrossRefGoogle Scholar
  23. 23.
    Di Giacomo AM, Biagioli M, Maio M. The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. Semin Oncol. 2010;37:499–507.CrossRefGoogle Scholar
  24. 24.
    Wang Y, Abu-Sbeih H, Mao E, et al. Endoscopic and histologic features of immune checkpoint inhibitor-related colitis. Inflamm Bowel Dis. 2018;24(8):1695–705.CrossRefGoogle Scholar
  25. 25.
    Choi K, Abu-Sbeih H, Samdani R, Nogueras Gonzalez G, Raju GS, Richards DM, et al. Can immune checkpoint inhibitors induce microscopic colitis or a brand new entity? Inflamm Bowel Dis. 2018.Google Scholar
  26. 26.
    Kim KW, Ramaiya NH, Krajewski KM, et al. Ipilimumab-associated colitis: CT findings. Am J Roentgenol. 2013;200:W468–74.CrossRefGoogle Scholar
  27. 27.
    Mitchell KA, Kluger H, Sznol M, Hartman DJ. Ipilimumab-induced perforating colitis. J Clin Gastroenterol. 2013;47:781–5.CrossRefGoogle Scholar
  28. 28.
    Singal AK, Jampana SC, Singal V, Kuo YF. Hepatocellular carcinoma predicts in-hospital mortality from acute variceal hemorrhage among patients with cirrhosis. J Clin Gastroenterol. 2012;46:613–9.CrossRefGoogle Scholar
  29. 29.
    Tarhini A, Lo E, Minor DR. Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. Cancer Biother Radiopharm. 2010;25:601–13.CrossRefGoogle Scholar
  30. 30.
    Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5:95.CrossRefGoogle Scholar
  31. 31.
    Hwang JH, Shergill AK, Acosta RD, et al. The role of endoscopy in the management of variceal hemorrhage. Gastrointest Endosc. 2014;80:221–7.CrossRefGoogle Scholar
  32. 32.
    Dadu R, Zobniw C, Diab A. Managing adverse events with immune checkpoint agents. Cancer J. 2016;22:121–9.CrossRefGoogle Scholar
  33. 33.
    Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev. 2016;44:51–60.CrossRefGoogle Scholar
  34. 34.
    Collins M, Michot JM, Danlos FX, et al. Inflammatory gastrointestinal diseases associated with PD-1 blockade antibodies. Ann Oncol. 2017;28:2860–5.CrossRefGoogle Scholar
  35. 35.
    Minor DR, Chin K, Kashani-Sabet M. Infliximab in the treatment of anti-CTLA4 antibody (ipilimumab) induced immune-related colitis. Cancer Biother Radiopharm. 2009;24:321–5.CrossRefGoogle Scholar
  36. 36.
    Johnson DH, Zobniw CM, Trinh VA, Ma J, Bassett RL Jr, Abdel-Wahab N, et al. Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis. J Immunother Cancer. 2018;6(1):103.CrossRefGoogle Scholar
  37. 37.
    Yang JC, Hughes M, Kammula U, et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother. 2007;30:825–30.CrossRefGoogle Scholar
  38. 38.
    Burdine L, Lai K, Laryea JA. Ipilimumab-induced colonic perforation. J Surg Case Rep. 2014;2014:rju010.CrossRefGoogle Scholar
  39. 39.
    Ananthakrishnan AN, Higuchi LM, Huang ES, et al. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann Intern Med. 2012;156:350–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of OncologyShanghai Dermatology Hospital, Tongji UniversityShanghaiChina
  2. 2.Tongji University Cancer Center, The Shanghai Tenth People’s Hospital, Tongji UniversityShanghaiChina
  3. 3.Department of Gastroenterology, Hepatology and Nutrition, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA

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