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Gastrointestinal and Hepatic Complications of Immunotherapy: Current Management and Future Perspectives

  • GI Oncology (R Bresalier Section Editor)
  • Published:
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Abstract

Purpose of Review

Checkpoint inhibitor (CPI) immunotherapy has transformed the treatment of multiple cancers over the past decade, leading to durable remissions, but also to severe inflammatory toxicities. These toxicities, termed immune-related adverse events (irAEs), can affect any organ system in the body, but commonly induce inflammation in barrier organs. Gastrointestinal (GI) and hepatic irAEs are among the most frequent and most severe from contemporary immunotherapies, with inflammation in the colon and or small intestines (entero)colitis as the single most common GI irAE. The aim of this review is to describe the evidence supporting our current understanding of CPI enterocolitis and hepatitis, as well as the management of these entities.

Recent Findings

Although most patients who develop enterocolitis recover without long-term GI sequelae, enterocolitis is still an important reason for treatment discontinuation, which, in patients with metastatic cancer, can be a life-threatening outcome. At present, we have almost no prospective, randomized data regarding the management of CPI enterocolitis, and current management algorithms are based on expert opinion and small retrospective studies with a high likelihood of bias. Retrospective studies have defined colonic ulceration as a predictor of colitis responsiveness to corticosteroids, and have defined microscopic colitis as a subtype of CPI enterocolitis with a distinct treatment response. Corticosteroids appear to be effective for 60–70% of patients with CPI enterocolitis, with about a third of patients requiring escalation to a biologic agent such as infliximab or vedolizumab. Yet proper sequencing of these treatments to minimize risk and maximize treatment benefit has not been established, and we do not know how treatment of colitis influences cancer outcomes.

Summary

CPI enterocolitis and hepatitis are important causes of treatment interruption and discontinue, and significant morbidity in patients undergoing immunotherapy. As guidelines for diagnosis and management rely heavily on expert opinion, we have an urgent need for randomized and prospective trials that use both colitis and cancer outcomes to determine optimal management strategies.

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Funding

This work was partially supported by a National Institutes of Health Mentored Clinical Scientist Development Award 1K08DK114563-01 and the American Gastroenterological Association Research Scholars Award.

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  1. Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA

    Michael Dougan

  2. Harvard Medical School, Boston, MA, USA

    Michael Dougan

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  1. Michael Dougan
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Correspondence to Michael Dougan.

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The author is a consultant for Tillotts Pharma, Partner Therapeutics, and Genentech-Roche, receives research funding from Novartis, and is on the Scientific Advisory Board for Neoleukin Therapeutics.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Dougan, M. Gastrointestinal and Hepatic Complications of Immunotherapy: Current Management and Future Perspectives. Curr Gastroenterol Rep 22, 15 (2020). https://doi.org/10.1007/s11894-020-0752-z

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