The field of cancer immunotherapy has exploded in recent years, with new therapies showing promising results for effective treatment of various cancer types. Immune checkpoint inhibitors (ICI) work by blocking checkpoint proteins that prevent breakdown of tumor cells by T-lymphocytes. Checkpoint proteins exist to prevent autoimmunity and destruction of healthy cells, but may allow tumor cells to grow unchallenged. Three checkpoint proteins – cytotoxic T-lymphocyte protein–4 (CTLA-4), programmed cell-death protein–1 (PD-1), and programmed cell-death protein ligand–1 (PDL-1) – arefor current ICIs.1
ICIs are used to treat various cancer types (e.g., lung, renal-cell, and Hodgkin’s lymphoma). Immune-related adverse events (irAE) arewith ICI use, ranging from 15% to 90%, and can occur at any point during, or even after, treatment.2
Immune checkpoint inhibitor–related gastrointestinal adverse reactions
GIare the second most common irAE, occurring in about 35%-50% of all reported irAEs.3 Anti-CTLA-4 medications have the highest association with GI irAE. The most common GI symptoms are diarrhea, abdominal pain, urgency, and nausea/vomiting. GI involvement can occur along the entirety of the GI tract – from the oral cavity to the colorectum. These are usually seen within 6-8 weeks of starting treatment, but can occur as early as 1 week after initiation or as late as 12 months after the last dose.2 Although colitis is the most common area of luminal inflammation, aphthous ulcers, esophagitis, gastritis, and enteritis can be seen. have the highest associated rate of diarrhea (33%-50%) and colitis (7%-22%) of all ICIs.4 Computed tomography (CT) may show colonic wall thickening or fat stranding, indicating inflammation. Endoscopically, the colon can appear grossly normal erythema, erosions, ulcerations, and/or loss of vascular pattern.5 Inflammation can be patchy or continuous. shows increased lamina propria cellularity, neutrophilic infiltration (intraepithelial or crypt abscesses), and increased crypt apoptosis.6
The liver, pancreas, gallbladder, and biliary tract can also be affected by irAE. The liver is most commonly involved (i.e. 5% of irAE), manifesting as asymptomatic liver chemistry elevation, particularly aminotransferases. This can progress to acute symptomatic hepatitis with jaundice, fever, or malaise, and rarely to fulminant hepatitis.