S4963 Pembrolizumab-Induced Immune Checkpoint Inhibitor Colitis

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy due to their ability to enhance the immune system’s recognition and destruction of cancer cells. While these medications have been utilized in the treatment of multiple malignancies including non-small cell lung cancer and melanoma, they can also trigger immune-mediated adverse events such as endocrinopathies, pneumonitis, and colitis. ICI-induced colitis, a rare adverse event, occurs 6-8 weeks after initiation of therapy, although there have been cases of delayed presentations. The presentation includes watery diarrhea, abdominal pain, rectal bleeding, or colonic perforation. In order to make the diagnosis of ICI-induced colitis, colonoscopy is performed to detect the presence of colitis. Case Description/Methods: A 76-year-old man with stage IV non-small cell lung cancer presented to the emergency department in May 2025 with abdominal pain and a 3 week history of watery, non bloody diarrhea. He denied recent travel, hospitalizations, dietary changes, or sick contacts. He was started on pembrolizumab December 2024 and had received his last infusion 2 weeks prior to the onset of his symptoms. His outpatient oncologist started him on prednisone 50 mg once daily, but eventually presented to the emergency department after his symptoms failed to resolve. On admission, GI polymerase chain reaction and Clostridium difficile testing were negative, and CT abdomen and pelvis showed wall thickening of the left hemicolon and ascending colon, suspicious for colitis. Fecal calprotectin was 3600 mcg/g, indicating inflammation. The patient was started on methylprednisolone 120 mg IV daily, and after 5 days, his symptoms improved. Colonoscopy showed evidence of mayo grade 2 colitis, while biopsies of the cecum, transverse, descending, and sigmoid colons showed evidence of active colitis, confirming the diagnosis of ICI-induced colitis. The patient was switched to prednisone with plans to follow up with his oncologist to further taper the steroids. Discussion: This case highlights the presentation, evaluation, and therapeutic approach to a rare ICI-associated adverse event. The rapid response to high-dose corticosteroids supports the current guidelines of using corticosteroids in moderate to severe cases of ICI-induced colitis. This case highlights the utility of promptly identifying ICI-induced colitis and the need for multidisciplinary coordination in the management of such cases to prevent long-term oncologic or gastrointestinal complications, while also balancing the patient’s cancer treatment goals.