EP731 - Immune Checkpoint Inhibitor Therapy after Ileoanal Pouch for Ulcerative Colitis: A Vulnerable Population for GI Toxicity?

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Purpose/Background: Background: Since their inception in 2011, the use of immune checkpoint inhibitors (ICIs) has expanded, and they are now FDA approved for the treatment of multiple cancers. ICIs are unique in that their efficacy and toxicity both arise from immune activation. Patients with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis may present a particular challenge as they may be at an increased risk of gastrointestinal (GI) adverse events with ICI treatment, which occurs in approximately 40% of cases overall. Currently, there is limited data on ICI toxicity in patients with IPAA for treatment of IBD. In this study, we reviewed a system-wide dataset to determine potential toxicity, and risks associated in this vulnerable patient population.

Methods/Interventions: We retrospectively reviewed an enterprise-wide dataset to identify patients who had undergone IPAA and subsequent ICI therapy. Patients without IBD and those with colonic J-pouches were excluded. Data were collected on demographics, baseline bowel symptoms, pouchitis history, and ICI therapy details including indication, dosage, and duration. Medical records were reviewed, and toxicity was graded using the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5). We documented the outcomes and treatments of patients who developed immune-related enteritis.

Results/Outcomes: Seven patients met inclusion criteria, including 3 females, with a median age of 71 years (range 68-74). Six (86%) patients underwent IPAA for medically refractory ulcerative colitis (UC), and one for UC-associated sigmoid cancer. Prior to surgery, 28% of the patients received any biologic therapy with the most common being infliximab (14.2%). No patients were on IBD advanced therapies (biologics or small molecules) during or immediately prior to ICI treatment. Three patients had a history of pouchitis treated with antibiotics prior to receiving ICI. Baseline bowel habits varied and ranged from to 5-10 motions per day. The indications for ICI therapy included colon cancer (n=1), hepatocellular carcinoma (n=1), non-small cell lung cancer (n=1), renal cell carcinoma (n=2), squamous cell carcinoma of the skin (n=1), and inflammatory breast cancer (n=1). Five patients received pembrolizumab, one atezolizumab, and one cemiplimab. A total of 5 (71%) of IPAA patients experienced no grade 3 GI toxicity, while 2 (29%) experienced grade 3 diarrhea/enteritis, leading to ICI cessation. Of these, both were treated with prednisone, one in combination with infliximab. One (14%) patient discontinued pembrolizumab due to acute tubular necrosis (ATN). Non-GI adverse events included hypothyroidism (n=1) and pruritus (n=1). Cancer response has been assessed in 5 patients and2 are still on ICI. Overall, 2 (29%) had stable disease and 2 (29%) had progression on pembrolizumab. One patient experienced tumor progression which was assessed after being switched to cabozantinib due to intolerance to atezolizumab.

Conclusion/Discussion: Overall, there was a similar rate of grade 3 GI toxicity in IPAA patients receiving ICI to what is reported in non-IPAA. Significant toxicity was not observed in the majority of this cohort, suggesting that IPAA patients are not at increased risk of adverse events with ICI therapy. However, given the small sample size of this study, further work is needed to validate our findings. As ICI therapy is more widely applied, it is critical that we continue to monitor for negative effects, particularly in potentially vulnerable patient populations.