Association of Chronic Immune-Mediated Diarrhea and Colitis With Favorable Cancer Response
Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas;
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Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China;
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Background: Immune-mediated diarrhea and colitis (IMDC) is a common immune-related adverse effect related to immune checkpoint inhibitors. We aimed to identify risk factors for chronic IMDC and its prognostic value in cancer outcomes. Methods: We retrospectively collected data on patients with a diagnosis of IMDC between January 2018 and October 2019 and grouped them based on disease duration into acute (≤3 months) and chronic (>3 months) categories. A logistic regression model and the Kaplan-Meier method with log-rank tests were used for biostatistical analysis. Results: In our sample of 88 patients, 43 were in the chronic group and 45 were in the acute group. Genitourinary cancer and melanoma accounted for 70% of malignancies. PD-1/L1 monotherapy (52%) was the more frequently used regimen. We showed that chronic IMDC was associated with proton pump inhibitor use (odds ratio [OR], 3.96; P=.026), long duration of IMDC symptoms (OR, 1.05; P<.001) and hospitalization (OR, 1.07; P=.043), a histologic feature of chronic active colitis (OR, 4.8; P=.025) or microscopic colitis (OR, 5.0; P=.045), and delayed introduction of selective immunosuppressive therapy (infliximab/vedolizumab; OR, 1.06; P=.047). Chronic IMDC also reflected a better cancer response to immune checkpoint inhibitors (30% vs 51%; P=.002) and was accompanied by improved overall survival (P=.035). Similarly, higher doses of selective immunosuppressive therapy were associated with better overall survival (P=.018). Conclusions: Chronic IMDC can develop among patients with a more aggressive disease course and chronic features on colon histology. It likely reflects a prolonged immune checkpoint inhibitor effect and is associated with better cancer outcome and overall survival.
Submitted June 25, 2020; final revision received August 11, 2020; accepted for publication August 31, 2020.
Published online December 14, 2020.
Author contributions: Study concept and design: Thomas, Y. Wang. Data collection: Zou. Conduct and interpretation of analysis: Zou. Project design: Abu-Sbeih, Ma, Peng. Interpretation of results: Thomas, Y. Wang. Preservation of data accuracy and integrity at all stages: Thomas, Y. Wang. Biostatistical analysis: Qiao. Manuscript preparation: Thomas, Y. Wang, Zou. Critical revision: Abu-Sbeih, Ma, Peng, J. Wang, Shah, Glitza Oliva, Piha-Paul, Thompson, Zhang.
Disclosures: Dr. Piha-Paul has disclosed that she receives grant/research support (through her institution) from AbbVie, Inc.; ABM Therapeutics, Inc.; Acepodia, Inc; Alkermes; Aminex Therapeutics; Amphivena Therapeutics, Inc.; BioMarin Pharmaceutical, Inc; Boehringer Ingelheim; Bristol-Myers Squibb; Cerulean Pharma, Inc.; Chugai Pharmaceutical Co., Ltd; Curis, Inc.; Daichi Sanko; Eli Lilly; ENB Therapeutics; Five Prime Therapeutics; Gene Quantum; Genmab A/S; GlaxoSmithKline; Helix BioPharma Corp.; Incyte Corporation; Jacobio Pharmaceuticals Co., Ltd.; Medimmune, LLC.; Medivation, Inc.; Merck Sharp & Dohme Corp.; Novartis Pharmaceuticals; Pieris Pharmaceuticals, Inc.; Pfizer; Principia Biopharma, Inc.; Puma Biotechnology, Inc.; Rapt Therapeutics, Inc.; Seattle Genetics; Silverback Therapeutics; Taiho Oncology; Tesaro, Inc.; and TransThera Bio. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: Dr. Piha-Paul is the recipient of an NCI/NIH Core Grant (P30CA016672 – CCSG shared resources).
Disclaimers: Ethics approval for this study was granted by The University of Texas MD Anderson Cancer Center Institutional Review Board (PA18-0472). Patient consent was waived for this study. The datasets used and analyzed in this study are available from the corresponding author upon reasonable request.
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