P0930 - Gastrointestinal Infection Prior to Immune Checkpoint Inhibition Hinders Treatment Efficacy and Increases the Risk for Checkpoint-Inhibitor Colitis

Malek Shatila, MD¹, Kian Abdul-Baki, DO², Andres Rivera, MD³, Kei Takigawa, MD³, Irene J. Lee, MD³, Andrew Sullivan, MD⁴, Tanvi Gupta, MD⁵, Linfeng Lu, MD³, Raakhi Menon, DO², Ayesha Khan, DO², Hamza Salim, MD², Elliot Axel. Baerman, MD³, Carolina Colli Cruz, MD⁶, Cristina M. Natha, MD⁵, Varun Vemulapalli, MD⁵, Garrett T. Coleman, ⁷, Krishnavathana Varatharajalu, MD¹, Yan Zhou, MD⁸, Hao Chi Zhang, MD⁶, Mehnaz A. Shafi, MD⁸, Yinghong Wang, MD, PhD^8
1The University of Texas MD Anderson Cancer Center, Houston, TX; ²University of Texas Medical Branch, Galveston, TX; ³Baylor College of Medicine, Houston, TX; ⁴University of Texas Health Science Center, Houston, TX; ⁵University of Texas Health, McGovern Medical School, Houston, TX; ⁶MD Anderson Cancer Center, Houston, TX; ⁷University of Texas Medical Branch, John Sealy School of Medicine, Galveston, TX; ⁸University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: The gut microbiome has received increasing attention in recent years for its role in cancer responsiveness to treatment and treatment-related toxicities. Gastrointestinal (GI) infections often arise due to and cause intestinal dysbiosis, which can impact immune checkpoint inhibitor (ICI) efficacy and increase the risk of adverse effects such as colitis. Our study aims to explore the impact of GI infection prior to ICI initiation on the incidence and severity of immune-mediated colitis (IMC) as well as on patient survival.

Methods: This was a single center, retrospective review including all patients who received ICIs between 01/2010 to 02/2024 and developed IMC. Patients were screened for IMC based on stool tests, then divided into two groups depending on their history of GI infection within three months prior to ICI initiation. We collected patient demographic, and IMC and GI infection-related clinical data.

Results: 1,132 patients met the study criteria and were included, 34 of whom had a history of GI infection prior to ICI. GI infections were most commonly caused by Clostridiodes difficile and treated with oral antibiotics for a median of 10 days (IQR: 7-14 days). The incidence of IMC was increased within this subgroup, with 8.7% (34/393) of patients with prior GI infection developing colitis compared to 5.1% (1098/21,736) of those without (p=0.002). IMC symptoms and severity were similar between both groups, as were outcomes such as hospitalization, symptom resolution, and recurrence rates (p >0.05). Treatments used in both groups did not differ significantly, with the exception of fecal microbiota transplantation (FMT), which was used more in the prior infection group (p=0.029). Outcomes of FMT-treated patients with or without prior GI infection did not differ significantly (p >0.05). Finally, on multivariate Cox survival analysis, prior GI infection was independently associated with mortality (OR: 1.6, CI:1.4-1.8; p< 0.001) among ICI-treated patients after controlling for age, sex, and race.

Discussion: Our study is the first to explore the impact of GI infection prior to ICI initiation on IMC risk and patient survival. GI infection may interfere with ICI efficacy as reflected by worse overall survival among these patients and may increase the risk of developing IMC. These findings may be due to the association of GI infection with dysbiosis of the gut microbiome. Further studies with a larger study group are needed to validate these results.



Disclosures:


Malek Shatila, MD¹, Kian Abdul-Baki, DO², Andres Rivera, MD³, Kei Takigawa, MD³, Irene J. Lee, MD³, Andrew Sullivan, MD⁴, Tanvi Gupta, MD⁵, Linfeng Lu, MD³, Raakhi Menon, DO², Ayesha Khan, DO², Hamza Salim, MD², Elliot Axel. Baerman, MD³, Carolina Colli Cruz, MD⁶, Cristina M. Natha, MD⁵, Varun Vemulapalli, MD⁵, Garrett T. Coleman, ⁷, Krishnavathana Varatharajalu, MD¹, Yan Zhou, MD⁸, Hao Chi Zhang, MD⁶, Mehnaz A. Shafi, MD⁸, Yinghong Wang, MD, PhD⁸. P0930 - Gastrointestinal Infection Prior to Immune Checkpoint Inhibition Hinders Treatment Efficacy and Increases the Risk for Checkpoint-Inhibitor Colitis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.