Gastrointestinal Toxicities of Immune Checkpoint Inhibitors Are Associated With Enhanced Tumor Responsiveness and Improved Survival

Mohammad Alomari; Suleiman Al Ashi; Pravallika Chadalavada; Shrouq Khazaaleh; Fahrettin Covut; Laith Al Momani; Ahmed Elkafrawy; Vinay Padbidri; Pauline Funchain; Donald Campbell; Carlos Romero-Marrero

doi:10.14740/gr1491

Gastrointestinal Toxicities of Immune Checkpoint Inhibitors Are Associated With Enhanced Tumor Responsiveness and Improved Survival

Gastroenterology Res. 2022 Apr;15(2):56-66. doi: 10.14740/gr1491. Epub 2022 Mar 12.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA.
² These authors contributed equally to this work.
³ Internal Medicine-Hospitalist Department, University of Nebraska Medical Center, Omaha, NE, USA.
⁴ Department of Internal Medicine, Cleveland Clinic Fairview Hospital, Cleveland, OH, USA.
⁵ Department of Gastroenterology and Hepatology, University of Missouri-Kansas City, Kansas City, MO, USA.
⁶ Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, OH, USA.
⁷ Department of Hematology & Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA.

PMID: 35572476
PMCID: PMC9076156
DOI: 10.14740/gr1491

Abstract

Background: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced malignancies. However, they are associated with the development of multiple gastrointestinal immune-related adverse events (GI-irAEs). We aimed to evaluate the types and severity of GI-irAEs associated with ICI therapy, to identify potential risk factors for developing GI-irAEs and to determine the relationship of GI-irAEs development to tumor responsiveness and overall survival.

Methods: All patients who received ICIs for advanced malignancies at our center were included. Medical records were reviewed, and data extraction included: baseline demographic characteristics, immunotherapy regimens, development of GI-irAEs, response to treatment, and overall survival. Overall survival was calculated from the date of treatment initiation and estimated by the Kaplan-Meier method.

Results: Five hundred sixty-seven patients received ICI therapy for stage IV malignancies. Forty-one (7%) patients experienced at least one GI-irAE. Among those experiencing GI-irAEs, 23 (56%) developed hepatitis, 17 (42%) developed colitis, four (10%) developed pancreatitis, and two (5%) developed gastritis. Patients who developed GI-irAEs experienced a better response to ICI therapy compared to patients who did not develop GI-irAEs (41% vs. 27%, P = 0.003). The 2-year overall survival rate of stage IV cancer patients who developed GI-irAEs was 62% (95% confidence interval (CI): 49 - 79) and 36% for those who did not develop GI-irAEs (95% CI: 32 - 41) (P = 0.002). The median follow-up time of surviving patients was 28 months. Twelve (29%) of the patients receiving dual ICI therapy developed GI-irAEs.

Conclusion: Hepatitis, colitis, and pancreatitis were the most commonly encountered GI-irAEs with ICI therapy. Development of these GI-irAEs was associated with superior tumor responsiveness and better overall survival.

Keywords: Cancer; Gastrointestinal toxicities; Immune checkpoint inhibitors; Immune-related adverse events; Survival; Tumor response.