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Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors

Abstract

Immune-related adverse events (IrAEs) affecting the gastrointestinal (GI) tract and liver are among the most frequent and most severe inflammatory toxicities from contemporary immunotherapy. Inflammation of the colon and or small intestines (entero)colitis is the single most common GI IrAE and is an important cause of delay of discontinuation of immunotherapy. The severity of these GI IrAEs can range from manageable with symptomatic treatment alone to life-threatening complications, including perforation and liver failure. The frequency and severity of GI IrAEs is dependent on the specific immunotherapy given, with cytotoxic T lymphocyte antigen (CTLA)-4 blockade more likely to induce severe GI IrAEs than blockade of either programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1), and combination therapy showing the highest rate of GI IrAEs, particularly in the liver. To date, we have minimal prospective data on the appropriate diagnosis and management of GI IrAEs, and recommendations are based largely on retrospective data and expert opinion. Although clinical diagnoses of GI IrAEs are common, biopsy is the gold standard for diagnosis of both immunotherapy-induced enterocolitis and hepatitis and can play an important role in excluding competing, though less common, diagnoses and ensuring optimal management. GI IrAEs typically respond to high-dose corticosteroids, though a significant fraction of patients requires secondary immune suppression. For colitis, both TNF-α blockade with infliximab and integrin inhibition with vedolizumab have proved highly effective in corticosteroid-refractory cases. Detailed guidelines have been published for the management of low-grade GI IrAEs. In the setting of more severe toxicities, involvement of a GI specialist is generally recommended. The purpose of this review is to survey the available literature and provide management recommendations focused on the GI specialist.

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Acknowledgments

Professor BL Rapoport is supported by the Cancer Association of South Africa (CANSA) and the National Research Foundation (NRF) of South Africa. Dr. I. Glezerman is supported by the NIH/NCI (Cancer Center Support Grant P30 CA008748).

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All of the authors contributed equally to the conceptualization of the manuscript; MD drafted the manuscript, while BLR and DBJ provided clinical input and BLR, DBJ, and RA editorial oversight. All of the authors provided critical appraisal of the manuscript and approve of its submission.

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Correspondence to Bernardo L. Rapoport.

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AB, RA, JC, TC, PG, DG, and VRS have no conflict of interest to declare. MD reports grants from Novartis and other (SAB) from Neoleukin Therapeutics, personal fees from Partner Therapeutics, personal fees from Tillotts Pharma, and grants from Genentech outside the submitted work. MG reports consultant work with Bristol Myers Squibb (BMS) and AstraZeneca outside the submitted work. IG reports other (Stock Ownership) from Pfizer Inc. and personal fees from CytomX Inc. outside the submitted work. DBJ reports other (advisory board) from Array Biopharma, grants and other (advisory board) from BMS, other (advisory board) from Jansen, grants from Incyte, other (advisory board) from Merck, and other (advisory board) from Novartis outside the submitted work. In addition, DBJ has a patent co-inventor on use of CTLA-4 agonist for IAEs pending. BLR reports personal fees and other (advisory board) from Merck and Co; grants, personal fees, and other (advisory board) from BMS; grants, personal fees, and other (advisory board) from Roche South Africa; and personal fees and other (advisory board) from AstraZeneca during the conduct of the study. MSA reports personal fees from Gilead, grants from Pfizer, and personal fees from Abbvie outside the submitted work.

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Dougan, M., Blidner, A.G., Choi, J. et al. Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors. Support Care Cancer 28, 6129–6143 (2020). https://doi.org/10.1007/s00520-020-05707-3

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Keywords

  • Checkpoint blockade
  • Colitis
  • Enterocolitis
  • Gastrointestinal immune-related adverse events
  • Hepatitis
  • Immune-related adverse events
  • Immunotherapy