Gastrointestinal Toxicity of Immunotherapy
Authors:
J. Špaček
Authors‘ workplace:
Onkologická klinika 1. LF UK a VFN v Praze
Published in:
Klin Onkol 2020; 33(1): 23-28
Category:
Review
doi:
https://doi.org/10.14735/amko202023
Overview
Immunotherapy is a standard modern therapeutic modality of clinical oncology. Due to the specific nature of affecting the immune system of the oncology patient, modern immunotherapy brings new and sometimes difficult to recognise autoimmune adverse reactions. One of the organ systems most commonly affected by autoimmune inflammation is the gastrointestinal system. The incidence of autoimmune enterocolitis in patients undergoing immunotherapy ranges from 1 to 25% depending on the type of drug administered (checkpoint inhibitor) and whether the patient is being treated with monotherapy or combination immunotherapy. The clinical signs (diarrhoea) and severity of gastrointestinal toxicity of immunotherapy are stratified on a four-step scale. The intensity of pharmacotherapy for these adverse events is determined by the degree of severity. Most side effects are reversible and well-managed with corticosteroid therapy. If symptoms are not relieved within 3–5 days with high doses of corticosteroids, immunosuppressive therapy with the anti-TNF inhibitor infliximab at 5 mg/kg should be given every 2 weeks until the signs of toxicity have disappeared. Early initiation of adequate corticotherapy for these auto-immune conditions induced by immunotherapy is essential to the success of this supportive therapy. Therefore, general awareness of the potential pitfalls of checkpoint inhibitor therapy should be well understood and anticipated. Just as we are looking for biomarkers to predict the effect of immunotherapy, we should also focus on research into predicting the toxicity of immunotherapy.
The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Keywords:
corticosteroids – immunotherapy – checkpoint inhibitors – autoimmune inflammation – enterocolitis
Sources
1. Graziani G, Tentori L, Navarra P. Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharmacol Res 2012; 65 (1): 9–22. doi: 10.1016/ j.phrs.2011.09.002.
2. Gupta A, De Felice KM, Loftus EV jr et al. Systematic review: colitis associated with anti-CTLA-4 therapy. Aliment Pharmacol Ther 2015; 42 (4): 406–417. doi: 10.1111/apt.13 281.
3. Hofmann L, Forschner A, Loquai C et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer 2016; 60: 190–209. doi: 10.1016/j.ejca.2016.02.025.
4. 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 (15): 2283–2289. doi: 10.1200/JCO.2005.04.5716.
5. Slovin SF, Higano CS, Hamid O et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol 2013; 24 (7): 1813–1821. doi: 10.1093/annonc/mdt107.
6. Kumar V, Chaudhary N, Garg M et al. Corrigendum: current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol 2017; 8: 49. doi: 10.3389/fphar.2017.00049.
7. Dubin K, Callahan MK, Ren B et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun 2016; 7: 10391. doi: 10.1038/ncomms10391.
8. Chaput N, Lepage P, Coutzac C et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol 2017; 28 (6): 1368–1379. doi: 10.1093/annonc/mdx 108.
9. Menzies AM, Johnson DB, Ramanujam S et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol 2017; 28 (2): 368–376. doi: 10.1093/annonc/mdw443.
10. Bowyer S, Prithviraj P, Lorigan P et al. Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. Br J Cancer 2016; 114 (10): 1084–1089. doi: 10.1038/bjc.2016.107.
11. 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 (4): 395–401. doi: 10.1093/ecco-jcc/jjv227.
12. Postow MA. Managing immune checkpoint-blocking antibody side effects. Am Soc Clin Oncol Educ Book 2015; 35: 76–83. doi: 10.14694/EdBook_AM.2015.35.76.
13.Marin-Acevedo JA, Harris DM, Burton MC. Immunotherapy-induced colitis: an emerging problem for the hospitalist. J Hosp Med 2018; 13 (6): 413–418. doi: 10.12788/jhm.2925.
14. Rawa T, Reguła J. Management of gastrointestinal toxicity from nivolumab therapy. Oncol Clin Pract 2017; 13 (5): 225–229. doi: 10.5603/OCP.2017.0026.
15. McCutcheon JL, McClain CM, Puzanov I et al. Infectious colitis associated with ipilimumab therapy. Gastroenterology Res 2014; 7 (1): 28–31. doi: 10.14740/gr594e.
16. Lankes K, Hundorfean G, Harrer T et al. Anti-TNF-refractory colitis after checkpoint inhibitor therapy: possible role of CMV-mediated immunopathogenesis. Oncoimmunology 2016; 5 (6): e1128611. doi: 10.1080/21 62402X.2015.1128611.
17. Dilling P, Walczak J, Pikiel P et al. Multiple colon perforation as a fatal complication during treatment of metastatic melanoma with ipilimumab – case report. Pol Przegl Chir 2014; 86 (2): 94–96. doi: 10.2478/pjs-2014-0017.
18. Burdine L, Lai K, Laryea JA. Ipilimumab-induced colonic perforation. J Surg Case Rep 2014; 86 (2): 94–96. doi: 10.1093/jscr/rju010.
19. Shah R, Witt D, Asif T et al. Ipilimumab as a cause of severe pan-colitis and colonic perforation. Cureus 2017; 9 (4): e1182. doi: 10.7759/cureus.1182.
20. Verschuren EC, van den Eertwegh AJ, Wonders J et al. Clinical, endoscopic, and histologic characteristics of ipilimumab-associated colitis. Clin Gastroenterol Hepatol 2016; 14 (6): 836–842. doi: 10.1016/j.cgh.2015.12. 028.
21. Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012; 30 (21): 2691–2697. doi: 10.1200/JCO.2012.41.6750.
22. Geukes Foppen MH, Rozeman EA, van Wilpe S et al. Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management. ESMO Open 2018; 3 (1): e000278. doi: 10.1136/esmoopen-2017-000278.
23. Jain A, Lipson EJ, Sharfman WH et al. Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis. World J Gastroenterol 2017; 23 (11): 2023–2028. doi: 10.3748/wjg.v23.i11.2023.
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): 1695–1705. doi: 10.1093/ibd/izy104.
25. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987; 317 (26): 1625–1629. doi: 10.1056/NEJM198712243172603.
26. van der Heide H, van den Brandt-Gradel V, Tytgat GN et al. Comparison of beclomethasone dipropionate and prednisolone 21phosphate enemas in the treatment of ulcerative proctitis. J Clin Gastroenterol 1988; 10 (2): 169–172. doi: 10.1097/00004836-198804000-00013.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2020 Issue 1
Most read in this issue
- Side Effects and Efficacy of Immunotherapy
- The Important Role of STAT3 in Chronic Lymphocytic Leukaemia Biology
- Immunotherapy-Associated Myocarditis
- Neurotoxicity and Immunotherapy