Outcomes of Immune Checkpoint Inhibitor-Mediated Colitis: Multicenter Cohort Study

Immune checkpoint inhibitor (ICI)-mediated colitis (IMC) is a common and serious toxicity. Multiple reports have described the clinical presentation and course of IMC based on limited data. This was a collaborative effort from several cancer institutes to investigate features and outcomes of IMC. This was a retrospective, cohort study of patients who received ICI and developed endoscopically/histologically confirmed IMC between 1/1/2011 and 12/31/2019. Multivariate logistic regression analyses were conducted to assess predictors of IMC recurrence and long duration of corticosteroids (> 60 days). A total of 674 patients were included. 383 patients were males (56.8%). Median age was 63 years. Melanoma was the most common cancer type (48.4%). Most patients (53.1%) received CTLA-4 inhibitor, as monotherapy or in combination with PD-(L)-1. Median time from ICI therapy to IMC was 61.5 days (31.8-126). IMC was grade 2 in 475 patients (71.3%), grade 3 in 177 (26.6%), and grade 4 in 14 (2.1%). On endoscopy, 153 patients (22.7%) had mucosal ulceration, 130 of patients had severe features (deep, large, or multiple ulcers); 336 patients (49.9%) had non-ulcerative inflammation. Most patients were admitted to the hospital for management of IMC (64.9%). Fifteen patients (2.5%) needed ICU-level of care. Corticosteroids were given to 576 patients (85.5%). Median length of corticosteroid therapy was 52 days. TNF inhibitors were given to 244 patients (36.2%). Ninety patients (13.4%) received vedolizumab. After resolution of symptoms, 201 patients (29.8%) had recurrent IMC. Predictors of IMC recurrence were days of hospitalization (P=0.003) , grade 4 IMC (P=0.001), and use of TNF inhibitor or vedolizumab (P=0.003). Factors associated with long (> 60 days) corticosteroid therapy were grade 3 IMC (P=0.049) and reception of infliximab or vedolizumab (P=0.044). Sixteen patients (2.4%) had colonic perforation, 7 of them underwent surgical resection of a part of the colon. No IMC-related death was recorded. In conclusion, IMC can lead to colonic perforation requiring surgical intervention and ICU admission. Higher grades of IMC or diarrhea and the use of TNF inhibitors or vedolizumab were associated with worse IMC outcomes, and therefore, patients with these features should be monitored closely and treated aggressively early in the course.

Name thesis:degree_name

M.S. (Master of Science)

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Bioinformatics (UMKC)

Grantor

University of Missouri--Kansas City

Year dc:date.issued

2022

Author dc:creator

• Abu-Sbeih, Hamzah

Advisor dc:contributor.advisor

• Gaddis, Monica Louise, 1955-

Handle dc:identifier.uri

https://hdl.handle.net/10355/90336

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/90336