Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management

Abstract

BackgroundImmune checkpoint inhibitors are successfully introduced as anticancer treatment. However, they may induce severe immune-related adverse events (irAEs). One of the most frequent irAEs is diarrhoea. The main objective of this study was to analyse symptoms (ie, grade of diarrhoea), endoscopic and histological features and response to management in immune checkpoint inhibition-related colitis (IRC).Patients and methodsWe retrospectively analysed patients who developed diarrhoea on checkpoint inhibition and therefore underwent an endoscopy and/or were treated with corticosteroids. Patients were treated between August 2010 and March 2016 for metastatic melanoma or non-small cell lung cancer. Severity of IRC was scored using the endoscopic Mayo score and the van der Heide score.ResultsOut of a cohort of 781 patients, 92 patients were identified who developed diarrhoea and therefore underwent an endoscopy and/or were treated with corticosteroids. Patients were treated with monotherapy anticytotoxic T-lymphocyte antigen-4, antiprogrammed death receptor-1 or a combination of both. All patients had symptoms of diarrhoea (grade 1: 16%; grade 2: 39% and grade 3: 44%). A complete colonoscopy was performed in 62 (67%) patients, of whom 42 (68%) had a pancolitis (≥3 affected segments). Ulcers were seen in 32% of endoscopies. There was no significant correlation between the grade of diarrhoea at presentation and endoscopic severity scores, the presence of ulcers or histological features. In 54 episodes of diarrhoea (56%), patients received one or more cycles infliximab for steroid-refractory colitis. Patients with higher endoscopic severity scores, ulcers and/or a pancolitis needed infliximab more often.ConclusionsThe correlation between grade of diarrhoea and endoscopic or histological features for severity of colitis is poor. Patients with higher endoscopic severity scores, ulcers or a pancolitis needed the addition of infliximab more often. Therefore, endoscopy may have value in the evaluation of the severity of IRC and may help in decision making for optimal management.

Enterocolitis due to immune checkpoint inhibitors: a systematic review

“…Two studies have reported features of chronic IBD such as mononuclear cell infiltration, granulomas, basal plasmacytosis and crypt abnormalities (atrophy, distortion, branching, budding) in 40% of the patients 24 26. This chronic inflammatory process was found to infiltrate the submucosa in 47% of the patients 24. Another study, however, did not find histological signs of chronic colitis 25.…”

“…Another study, however, did not find histological signs of chronic colitis 25. Apoptotic cells in crypt epithelium have been reported in 42% of patients 24. Microscopic colitis has also been diagnosed in patients treated with anti-CTLA-4 antibodies 25 44 45.…”

Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective

“…The incidence of GI side effects is reported to be higher and more severe in patients treated with CTLA-4 blocking antibodies as compared with patients receiving PD-1 receptor inhibitors 2 18 19. One of the studies reports that diarrhoea is seen in 35% of patients treated with CTLA-4, 17%–20% in anti-PD-1 and 44% in those treated with combination therapy 13. Another study has shown that treatment-related adverse events of grade 3 or 4 occurred in 16.3% of patients in the nivolumab (anti-PD-1) group, 55% of those in the nivolumab-plus-ipilimumab group (combination therapy) and 27.3% of those in the ipilimumab group (anti-CTLA-4 group), suggesting that the combination therapy increases the risk of irAEs more than either agent used alone 20.…”

Workup and Management of Immune-Mediated Colitis in Patients Treated with Immune Checkpoint Inhibitors

“…Common histological findings include an increase in lamina propria cellularity, patchy neutrophilic infiltrate, and in some cases, crypt abscesses. One research group reported an association between endoscopic features and the need for immune suppression beyond high‐dose corticosteroids . These endoscopic findings included the presence of edematous and erythematous mucosa in addition to mucosal ulceration.…”