Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2022; 28(39): 5750-5763
Published online Oct 21, 2022. doi: 10.3748/wjg.v28.i39.5750
Immune checkpoint inhibitor-mediated colitis is associated with cancer overall survival
Alexa R Weingarden, John Gubatan, Sundeep Singh, Tatiana Clorice Balabanis, Akshar Patel, Arpita Sharma, Aida Habtezion
Alexa R Weingarden, John Gubatan, Sundeep Singh, Tatiana Clorice Balabanis, Akshar Patel, Arpita Sharma, Aida Habtezion, Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, United States
Author contributions: Weingarden AR and Habtezion A designed the research study; Weingarden AR, Balabanis T, Patel A, and Sharma A performed data collection; Gubatan J analyzed data; Weingarden AR, Gubatan J, Singh S, and Habtezion A wrote and edited the manuscript; all authors have read and approve the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Stanford University (Approval No. IRB 57125).
Conflict-of-interest statement: None of the authors have any potential conflicts of interest to disclose.
Data sharing statement: Data availability upon request from authors.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alexa R Weingarden, MD, PhD, Academic Fellow, Consultant Physician-Scientist, Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Alway Building, Room M211, 300 Pasteur Drive, Stanford, CA 94305, United States. aweingar@stanford.edu
Received: July 2, 2022
Peer-review started: July 2, 2022
First decision: August 1, 2022
Revised: September 24, 2022
Accepted: October 10, 2022
Article in press: October 10, 2022
Published online: October 21, 2022
ARTICLE HIGHLIGHTS
Research background

Immune checkpoint inhibitor-mediated colitis (IMC) is a common immune-related side effect (irAE) of checkpoint inhibitor treatment for cancer. Prior work has suggested that IMC may be associated with increased survival from cancer.

Research motivation

We sought to determine if IMC was associated with increased overall survival (OS) in a cohort of patients at our institution. These findings could expand existing data on IMC and cancer outcomes and might suggest a common immunological underpinning between the efficacy of checkpoint inhibitors and certain irAEs.

Research objectives

We performed a retrospective case-control study of individuals treated with immune checkpoint inhibitors at our institution who developed IMC, closely matched to a cohort of patients treated with checkpoint inhibitors without IMC. Using univariate and multivariate logistic regression, we determined significant clinical predictors of IMC and the association of presence of IMC on OS.

Research methods

We found that IMC was significantly associated with a higher OS as well as OS greater than 12 mo. In contrast to previous findings, vitamin D supplementation was significantly associated with development of both IMC and severe IMC. However, prior treatment with immune-enhancing medications was significantly associated with decreased risk of IMC.

Research results

In multivariate logistic regression analysis, IMC was significantly associated with a higher OS but not PFS. IMC was significantly associated with OS greater than 12 mo. Vitamin D supplementation was associated with increased risk of IMC.

Research conclusions

Our findings lend strength to the idea that IMC is associated with improved cancer outcomes with checkpoint inhibitor treatment. This may suggest common immunologic underpinnings between IMC and the anti-tumor effects of checkpoint inhibitors. These results also emphasize the importance of involving gastroenterologists with the management of IMC.

Research perspectives

Future research in this area should seek to expand current knowledge of the relationship between IMC and cancer survival. In particular, future work should focus on broadening the type and number of patients treated with immune checkpoint inhibitors and on tracking patients prior to initiating checkpoint inhibitors to determine if this relationship remains significant prospectively.