Fangwen Zou1,2, Hamzah Abu-Sbeih3, Weijie Ma2,4, Yuanzun Peng5, Wei Qiao6, Jianbo Wang7, Amishi Y Shah7, Isabella C Glitza Oliva8, Sarina A Piha-Paul9, John A Thompson10, Hao Chi Zhang2, Anusha S Thomas2, Yinghong Wang2. 1. 1Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China. 2. 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3. 3Department of Internal Medicine, University of Missouri, Kansas City, Missouri. 4. 4Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. 5. 5Department of Biosciences, Rice University, Houston, Texas. 6. 6Department of Biostatistics. 7. 7Department of Genitourinary Medical Oncology. 8. 8Department of Melanoma Medical Oncology, and. 9. 9Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas; and. 10. 10Department of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Abstract
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.
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.
Authors: Fangwen Zou; David Faleck; Anusha Thomas; Jessica Harris; Deepika Satish; Xuemei Wang; Aline Charabaty; Marc S Ernstoff; Isabella C Glitza Oliva; Stephen Hanauer; Jennifer McQuade; Michel Obeid; Amishi Shah; David M Richards; Elad Sharon; Jedd Wolchok; John Thompson; Yinghong Wang Journal: J Immunother Cancer Date: 2021-11 Impact factor: 13.751