Immune checkpoint inhibitor-mediated colitis is associated with cancer overall survival

doi:10.3748/wjg.v28.i39.5750

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Oct 21, 2022 (publication date) through Mar 4, 2026

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World Journal of Gastroenterology

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1007-9327

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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.

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
Processing time: 107 Days and 14.2 Hours

Abstract

BACKGROUND

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event following immune checkpoint inhibitor (ICI) therapy for cancer. IMC has been associated with improved overall survival (OS) and progression-free survival (PFS), but data are limited to a single site and predominantly for melanoma patients.

AIM

To determine the association of IMC with OS and PFS and identify clinical predictors of IMC.

METHODS

We performed a retrospective case-control study including 64 ICI users who developed IMC matched according to age, sex, ICI class, and malignancy to a cohort of ICI users without IMC, from May 2011 to May 2020. Using univariate and multivariate logistic regression, we determined association of presence of IMC on OS, PFS, and clinical predictors of IMC. Kaplan-Meier curves were generated to compare OS and PFS between ICI users with and without IMC.

RESULTS

IMC was significantly associated with a higher OS (mean 24.3 mo vs 17.7 mo, P = 0.05) but not PFS (mean 13.7 mo vs 11.9 mo, P = 0.524). IMC was significantly associated with OS greater than 12 mo [Odds ratio (OR) 2.81, 95% confidence interval (CI) 1.17-6.77]. Vitamin D supplementation was significantly associated with increased risk of IMC (OR 2.48, 95%CI 1.01-6.07).

CONCLUSION

IMC was significantly associated with OS greater than 12 mo. In contrast to prior work, we found that vitamin D use may be a risk factor for IMC.

Keywords: Immune checkpoint inhibitors; Immune checkpoint inhibitor-mediated colitis; Immune-related adverse events

Core Tip: Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event following immune checkpoint inhibitor (ICI) therapy for cancer. We sought to determine the association of IMC with overall survival (OS) and progression-free survival (PFS) among cancer patients treated with ICI and identify clinical predictors of IMC. We performed a retrospective case-control study including 64 ICI users who developed IMC. 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.