Gastrointestinal and liver adverse effects of anti-tumoral immune therapy: from recognition to treatment
Gastroenterology and Hepatology from Bed to Bench,
26 April 2021
Anti-tumoral immune therapy consists of monoclonal antibodies that target intra-cellular immune checkpoints—which under normal circumstances, act as regulators of T-cell immunity. By serving as inhibitors of cellular checkpoints, monoclonal antibodies stimulate the immune system thus augmenting the body’s response against cancer. These immune-enhancers or stimulators have revolutionized the treatment of malignancy as they continue to show improvement in the overall survival of cancer patients. Currently, in the United States, six immune checkpoint inhibitors are approved for the treatment of a variety of solid tumors (1). As these checkpoint inhibitors are relatively new, only a scant amount of literature is available regarding both their adverse effects and management thereof. In addition, as newer antibodies are being developed, and expected to be enlisted among the armamentarium of cancer chemotherapeutic agents—the need to understand their toxicity and adverse effects is of paramount importance. Herein, we review some of the gastrointestinal and liver sequelea secondary to the usage of immunotherapeutic checkpoint inhibitor agents in cancer chemotherapy, as well as present the diagnosis and recommended treatment strategies for their adverse effects.
Keywords: Anti-tumoral immune therapy, Treatment, Gastrointestinal and liver diseases.
(Please cite as: Weissman S, Saleem S, Al-Dulaimi D. Gastrointestinal and Liver adverse effects of anti-tumoral immune therapy: from recognition to treatment. Gastroenterol Hepatol Bed Bench 2021;14(3):195-199).
- immune checkpoint inhibitors
- adverse effects
Administration, USFDA. FDA approved drug products. 2017. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125377.
Cameron F, Whiteside G, Perry C. Ipilimumab: first global approval. Drugs 2011;71:1093-104.
Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol 2018; 4:1721-28
Puzanov I, Diab A, Abdallah K, Bingham CO 3rd, Brogdon C, Dadu R, 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.
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med,. 2010;363:711-23.
Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 2010;11:155-64.
Klair JS, Girotra M, Hutchins LF, Caradine KD, Aduli F, Garcia-Saenz-de-Sicilia M. Ipilimumab-induced gastrointestinal toxicities: a management algorithm. Dig Dis Sci 2016;61:2132–2139.
Gonzalez RS, Salaria SN, Bohannon CD, Huber AR, Feely MM, Shi C. PD-1 inhibitor gastroenterocolitis: case series and appraisal of 'immunomodulatory gastroenterocolitis'. Histopathology 2017;70:558–67.
Zhou W, Huang Y, Lai J, Lu J, Feely M, Liu X. Anti-Inflammatory Biologics and Anti-Tumoral Immune Therapies-Associated Colitis: A Focused Review of Literature. Gastroenterol Res 2018;11:174–188.
Marthey L, Mateus C, Mussini C, Nachury M, Nancey S, Grange F, et al. Cancer Immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis 2016;10:395–401.
Pagès C, Gornet JM, Monsel G, Allez M, Bertheau P, Bagot M, et al. Ipilimumab-induced acute severe colitis treated by infliximab. Melanoma Res 2013;23:227-30.
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.
Merrill SP, Reynolds P, Kalra A, Biehl J, Vandivier RW, Mueller SW. Early administration of infliximab for severe ipilimumab-related diarrhea in a critically ill patient. Ann Pharmacother 2014;48:806-10.
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; 6:103.
Mir R, Shaw HM, Nathan PD. Mycophenolate mofetil alongside high-dose corticosteroids: optimizing the management of combination immune checkpoint inhibitor-induced colitis. Melanoma Res 2019;29:102-106.
Abu-Sbeih H, Ali FS, Alsaadi D, Jennings J, Luo W, Gong Z, Richards DM, et al. Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor-induced colitis: a multi-center study. J Immunother Cancer 2018;6:142.
Wang Y, Wiesnoski DH, Helmink BA, Gopalakrishnan V, Choi K, DuPont HL, et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Nat Med 2018; 24:1804-8.
Weber J, Thompson JA, Hamid O, Minor D, Amin A, Ron I, Ridolfi R, et al. A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res 2009; 15:5591-8.
Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012; 30:2691-7.
Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol 2013; 31:616-22.
Bernardo SG, Moskalenko M, Pan M, Shah S, Sidhu HK, Sicular S, et al. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma. Melanoma Res 2013;23:47-54.
Hammers HJ, Plimack ER, Infante JR, Rini BI, McDermott DF, Lewis LD, et al. Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). J Clin Oncol 2014; 32S: ASCO #4504.
OPDIVO U.S. Prescribing Information. Available from: http://packageinserts.bms.com/pi/pi_opdivo.pdf. [Accessed on December 23, 2014]
Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369:134-44.
Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364:2517-26.
Kim KW, Ramaiya NH, Krajewski KM, Jagannathan JP, Tirumani SH, Srivastava A, et al. Ipilimumab associated hepatitis: imaging and clinicopathologic findings. Invest New Drugs 2013; 31:1071-7.
Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med 2013; 368:1365-6.
Important Safety Information about YERVOY® (ipilimumab). Available from: https://www.hcp.yervoy.com/pdf/rems-management-guide.pdf.
- Abstract Viewed: 0 times
- PDF Downloaded: 0 times