98 A Bio-Experienced Patient With Crohn’s Disease and Recurrent Cutaneous Squamous Cell Carcinoma Develops Immune Checkpoint Inhibitor Colitis

Background: Immune Checkpoint Inhibitors (ICIs) are used as primary immunotherapy in many cancers including skin, lung, renal cell, cervical, urothelial, and gastric. While they have improved outcomes in these cancers, they are associated with toxicities including a variant of colitis that can mimic an IBD flare. In this report, we present a case of suspected ICI-induced colitis in a patient with Crohn’s disease and recurrent cutaneous squamous cell carcinoma (SCC). Methods: A 56-year-old female with a history of stricturing and penetrating ileocolonic Crohn’s Disease and cutaneous SCC presented to the clinic with a chief complaint of severe bloody diarrhea. For review, the patient was diagnosed with Crohn’s disease at age 28 but remained off therapy due to a desire to pursue alternative treatments. This became clinically consequential when she developed a flank abscess and an associated enterocutaneous fistula near the ileocecal valve with terminal ileal (TI) stricture. Following drainage and antibiotics, biologic therapy was recommended. She deferred treatment for another 2 years before starting infliximab (IFX). She had partial response to IFX with mild improvement in fistula drainage, but a similar endoscopic appearance compared to pre-treatment colonoscopy. Given severe stenosis of the TI, surgery was recommended but the patient deferred. One year ago, she developed a left forearm SCC. She underwent excision and radiation but unfortunately developed local recurrence. A multidisciplinary discussion between the patient, gastroenterologist, and oncologist resulted in discontinuation of IFX and coordination of urgent ileocecal resection and fistula takedown. Following surgery, the patient experienced symptomatic remission from her Crohn’s disease, allowing initiation of pembrolizumab. Results: During the fourth round of immunotherapy, the patient developed bloody diarrhea, abdominal pain, and weight loss, suspicious for ICI-induced colitis. Pembrolizumab was discontinued and prednisone started. However, with minimal response to steroids, she started on risankizumab. She received one of 3 planned induction infusions but continued to have profuse diarrhea and expressed a strong preference to switch to vedolizumab (VDZ). Through shared decision-making, she was transitioned to VDZ. At follow-up after 2 VDZ induction doses, she reported marked improvement in her GI symptoms. Fortunately, despite not completing the intended 6-rounds of pembrolizumab, recent PET scan showed complete remission. Conclusions: In patients with IBD, treatment with an ICI increases the risk of flare and consideration of alternate chemo/immunotherapeutic options is made with risk/benefit analysis. A meta-analysis demonstrated that 40% of patients with IBD experienced a flare with ICI treatment with 76% requiring steroids and 37% requiring biologics. The clinical and endoscopic features of IBD and ICI colitis are similar, and management is guided by the degree of severity with severe cases often requiring discontinuation of the ICI, steroids, and biologics. Ruling out infectious causes of colitis and endoscopic evaluation are recommended prior to treatment. There is no consensus guidance on therapy selection for steroid-refractory ICI colitis in bio-experienced IBD patients; there is evidence for the efficacy of multiple drug classes commonly used in IBD including anti-TNFs, anti-integrins, JAK inhibitors, and IL-12/IL-23 inhibitors. Shared decision-making discussions between patient and provider are ultimately the best guide for treatment selection.