Abstract 5988: Microscopic colitis - rare events secondary to immune checkpoint inhibitors therapy

Abstract Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of care for cancer treatment but are associated with immune-related adverse events (irAEs). The combination of Nivolumab and Relatlimab (N+R) was approved in March 2022 for the treatment of unresectable or metastatic melanoma. While colitis is a well-known toxicity of ICIs, microscopic colitis (MC) presenting as watery diarrhea with normal endoscopic mucosal appearance, has not yet been described in Summary of Product Characteristics of N and R. Description: We present the case of a 54-year-old man undergoing treatment with N+R for recurrent BRAFV600Emt cutaneous malignant melanoma with metastases to soft tissues and lymph nodes. Eight weeks after starting therapy, the patient developed grade 3 (per CTCAE v.5) watery diarrhea. Stool tests were negative for infectious agents, including Clostridium difficile. Abdominal imaging with computed tomography did not reveal any signs of colitis. However, due to elevated fecal calprotectin levels (12 times above normal) and N+R treatment, ir-colitis was diagnosed. Intravenous methylprednisolone at 1 mg/kg/day has been administered and led to a temporary reduction of symptoms to grade 1. However, within a week, watery diarrhea worsened again to grade 3 despite ongoing steroid therapy. Due to steroid refractory, another immunomodulator was administered, including two doses of infliximab, without improvement. The patient did not lose weight. Colonoscopy revealed normal-appearing mucosa in the entire colon and terminal ileum. Random biopsies were done throughout the colon and terminal ileum. Histopathological examination revealed inflammatory infiltrates and focal increases in intraepithelial lymphocytosis, confirmed by CD3+ immunohistochemistry across all samples. The treatment with next-generation steroid budesonide (9 mg orally once daily in the morning) was administered, resulting in symptom resolution within two days. Diarrhea did not recur over the following four months. The N+R was finished. The patient received three doses of N+R and achieved a complete response (CR) on imaging, which is ongoing. Conclusion: Various types of colitis were found secondary to ICIs such as pseudomembranous, granulomatous, or collagenous with endoscopically visible changes in the mucosa. MC is suspected to result from increased immune activity in the gut mucosa. It can develop following ICIs therapy and presents with severe symptoms, often requiring hospitalization, steroids, and other immunomodulators. This case highlights that a normal mucosal appearance on colonoscopy does not exclude immune-mediated colitis. Next-generation steroids, such as budesonide, can be effective in managing MC during immunotherapy. Raising awareness of the uncommon irAEs is essential, as some rare events can lead to fatal outcomes. Radiological, endoscopic, and microscopic pictures will be presented on the poster. Citation Format: Barbara Radecka, Michał Piątek, Jacek Pawełczak, Ewa Stobiecka, Krystian Kowalczyk, Patryk Zając. Microscopic colitis - rare events secondary to immune checkpoint inhibitors therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5988.