Chronic gastrointestinal immune-related adverse events in patients exposed to immune checkpoint inhibitors

Background and aims: Immune checkpoint inhibitors (ICI) cause acute gastrointestinal (GI) immune-related adverse events (IrAEs). We aimed to report and describe chronic GI IrAEs. Methods: We included consecutive patients addressed to a single center between October 2010 and March 2022 for endoscopic and/or histological GI inflammation persisting at least six months after the last dose of ICI. Results: Among a total of 178 patients addressed for GI IrAE, 14 met the inclusion criteria (8 %). The median follow-up was 13 months after discontinuation of ICI. The most common symptom was watery diarrhea (54 %). Ten (77 %) patients had colonic involvement and three patients (21 %) had ileal involvement. Ten patients (77 %) had inflammatory lesions, two patients (15 %) had fistulas and one patient had (8 %) a stricture. All patients had lymphoplasmacytic infiltrate and basal plasmacytosis, and seven (54 %) had crypt distortions. Nine patients (69 %) received medical therapy, including five patients treated with vedolizumab, two patients (15 %) underwent intestinal resection. At the last follow-up, seven of the 13 patients were receiving maintenance therapy. Endoscopic lesions persisted one year after discontinuing ICI in 4/6 patients, and two years after discontinuation in 3/4 patients. Conclusions: Chronic GI IrAEs exist after ICI use.