Characteristics, treatment and outcome of patients with bowel perforation after immune checkpoint inhibitor exposure

Abstract

Abstract Purpose: Exposure to immune checkpoint inhibitors (ICIs) can predispose to immune-related adverse events (irAEs) involving the gastrointestinal tract. The association between ICIs and bowel perforation has not been well studied. We aimed to describe the clinical course, complications, treatment and outcomes of patients experiencing bowel perforation during or after ICI treatment. Methods: This retrospective, single-center study included adult cancer patients with bowel perforation that occurred between the first dose of ICI treatment and up to 1 years thereafter between 1/1/2010 and 4/30/2021. Patients’ clinical course, imaging, treatment and outcomes related to bowel perforation were collected and analyzed. Results: Of the 13,991 patients who received ICIs during the study period, 90 (0.6%) met the inclusion criteria. A majority were male (54.4%), the most common cancer type was melanoma (23.3%), and most patients had received PD-1/L1 inhibitor treatment (58.8%). Onset of perforation occurred after a median of 4 ICI treatment cycles. The most common symptom was abdominal pain (95.5%). The colon was the most common location for the perforation (37.7%). Evidence of diverticulitis, enterocolitis, or appendicitis was seen in 32 (35.6%) patients, and 6 (6.6%) patients had luminal cancer involvement at the time of perforation. The overall hospitalization rate related to perforation was 95.5%, with mortality of 15.5% during the same admission. Antibiotics were given in 95% of our sample; 37.8% of patients also required surgical/interventional radiology intervention. Forty-six patients (51.1%) had perforation-related complications (e.g. sepsis, fistula, abscess), which were associated with a higher mortality rate (30%). Conclusion: Our findings suggest a low incidence of bowel perforation after ICI treatment (0.6%), with 40% of patients having coexisting bowel inflammation as a potential contributing factor. Patients with bowel perforation had an aggressive disease course and high rates of hospitalization, complications and mortality. Early recognition and prompt intervention is critical to improve patient outcomes. Future studies are warranted to further investigate the cause, predictive markers and optimal treatment for this patient population.