S82 CAR T-Cell Therapy Associated With Onset of Inflammatory Bowel Disease Requiring Long-Term Advanced Therapy for Control of Chronic Ileocolitis

Background: Chimeric antigen receptor (CAR) T-cell therapy is a novel treatment for a broad spectrum of malignant conditions however complications are still being defined. Case reports have been published on enterocolitis similar to inflammatory bowel disease (IBD) with CAR T-cells affecting the gut mucosa. Reports are limited regarding chronic IBD requiring prolonged therapy. We present a case of IBD with CAR T-cell therapy requiring chronic advanced therapy with recurrent inflammation after discontinuation of bowel directed therapy. Methods: A 19-year-old male with history of acute lymphoblastic leukemia treated with CAR T-cell therapy developed unexplained diarrhea. Diagnosis of Crohn’s disease (CD) was made after CAR T-cell therapy by EGD and colonoscopy which showed aphthous ulcers scattered throughout colon and terminal ileum as well as gastritis. Pathology showed focal erosion in ileum, focal colitis consistent with Crohn’s disease, and gastritis. Initial therapy was Exclusive Enteral Nutrition which was not tolerated, and no response to off-label mesalamine. There was concern for initiation of tumor necrosis factor alpha (TNF-a) inhibitor given history of malignancy, age, and CAR T-cell therapy requiring intravenous immunoglobulin (IVIG) infusions every 6 weeks. Due to refractory symptoms, Adalimumab (ADA) was started with standard loading dose followed by 40 mg every 2 weeks with improvement in symptoms. Patient remained in endoscopic and histologic remission for 3 years with EGD and colonoscopy showing no evidence of recurrence on ADA. There was discussion regarding de-escalation of therapy and ADA was discontinued. Within 6 months, symptoms returned with diarrhea, hematochezia, and weight loss. EGD and colonoscopy demonstrated duodenal erosions and colitis. ADA was restarted with reload and maintenance 40 mg every 2 weeks with resolution of symptoms. No significant elevation in biomarkers on ADA with ESR 15, CRP 0.27, fecal calprotectin 109. Surprisingly, routine labs showed hepatitis B surface antibody and core antibody positive, otherwise unremarkable hepatitis serologies and synthetic function, despite previously negative hepatitis B serologies prior to CAR T-cell therapy. These findings may be due to IVIG infusions with passive transfer of antibodies. However, reactivation of hepatitis B is possible. TNF-a inhibitor was discontinued with monitoring of hepatic function and hepatitis B viral DNA levels. Results: Therapy was switched from ADA to interleukin-23 (IL-23) inhibitor Risankizumab (RZA) with standard induction followed by 360 mg every 8 weeks. IL-23 inhibitor was chosen with shared decision-making to minimize malignancy risk and mitigate potential reactivation of hepatitis B. Intestinal ultrasound (IUS) after induction of RZA demonstrated normal bowel wall and terminal ileum thickness. Conclusions: Inflammatory processes may result after CAR T-cell therapy. There is lack of guidance on IBD therapy with CAR T-cell therapy. Due to history of malignancy and hepatitis serologies, TNF-a inhibitor is a suboptimal choice. Anti-integrin therapy has been described for colitis associated with CAR T-cell therapy, however other therapies for new onset IBD may be considered. We demonstrate that our patient had clinical, endoscopic, and histologic findings of IBD after CAR T-cell therapy that responded to advanced therapy, relapsed with discontinuation of advanced therapy, and finally responded to additional advanced therapy with improved safety profile using shared decision-making.