Update on Immune Checkpoint Inhibitor Enterocolitis

Abstract

Purpose of Review Immune checkpoint inhibitor (ICI) therapy revolutionized the treatment of multiple solid and hematologic malignancies. Yet, with it came profound inflammatory toxicities that mimic autoimmune diseases, termed immune-related adverse events (irAEs). Prominent among these is gastrointestinal inflammation, including a spectrum of gastritis, enteritis, and colitis. Here we synthesize an approach to immune checkpoint related enterocolitis (irEC) – including diagnostics and therapeutics – underpinned by new insights into the mechanism behind these phenomena. Recent Findings This review presents updated insights on how to approach irEC, including novel approaches to selective immunosuppressive therapy, the role of fecal microbiota transplant, and the underlying cellular mechanisms of irEC. Summary This review provides an update on irEC diagnosis and therapy, with considerations of new therapies and special patient populations. The field of gastrointestinal irAEs requires additional investigation, which will ultimately provide the tools required for patients to continue to receive life-saving ICI therapy.

Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions

“…Colitis, either occurring in isolation or in combination with enteritis, is the most common gastrointestinal toxicity from checkpoint inhibitors, though the frequency and severity of gastrointestinal toxicities is highly dependent on the specific pathway inhibited 32 . For example, CTLA‐4 blockade leads to severe colitis in approximately 10% of patients, whereas inhibition of PD‐1 or PD‐L1 leads to colitis in 2%–5% of patients.…”

“…For example, CTLA‐4 blockade leads to severe colitis in approximately 10% of patients, whereas inhibition of PD‐1 or PD‐L1 leads to colitis in 2%–5% of patients. The most severe and frequent colitis occurs in patients receiving dual ICI therapy blocking both CTLA‐4 and PD‐1 where gastrointestinal inflammation occurs in approximately 40% of patients and severe colitis occurs in nearly 20% 32 . Isolated enteritis or gastroenteritis occurs in approximately 20% of patients who present with gastrointestinal symptoms while on ICI therapy 32,33 .…”

“…The most severe and frequent colitis occurs in patients receiving dual ICI therapy blocking both CTLA‐4 and PD‐1 where gastrointestinal inflammation occurs in approximately 40% of patients and severe colitis occurs in nearly 20% 32 . Isolated enteritis or gastroenteritis occurs in approximately 20% of patients who present with gastrointestinal symptoms while on ICI therapy 32,33 . Other toxicities in the organs of digestion, including the liver, biliary tree, and pancreas, are less common than mucosal toxicities; these toxicities are nevertheless important causes of morbidity in these patients and have been reviewed elsewhere 34,35 …”

“…Patients can additionally have urgency, cramping and loss of continence 34 . Upper gastrointestinal tract symptoms such as nausea, vomiting, and decreased appetite are also fairly common, and can be associated with inflammation in the stomach and small intestines, though inflammation in the upper gastrointestinal tract can occur in patients who present with isolated diarrhea 32–34 . Probably the most striking difference between gastrointestinal irAEs and other forms of gastrointestinal inflammation is the disease course.…”

The evolving landscape of immune‐related adverse events that follow immune checkpoint immunotherapy in cancer patients

“…Although most of the GI irAEs are mild in nature, their high occurrence rate makes them the leading cause of severe toxicities associated with ICIs. In his review, he provides an in‐depth description of the clinical manifestations along with a thorough discussion of the immune mechanisms known to‐date (e.g., gut CD8 + TRMs) associated with ICI‐colitis, which is the most common GI toxicity associated with the use of ICIs 33 . He also discusses risk factors associated with ICI‐colitis, current standard of care, upcoming clinical trials, and the challenges related to the current lack of clinical trial data to guide management of patient care.…”