A109 CHECKPOINT INHIBITOR-RELATED LYMPHOCYTIC COLITIS: A NEW, PATHOLOGICAL ENTITY

Checkpoint inhibitors, such as anti-cytotoxic-T-lymphocyte antigen-4 (anti-CTLA-4) and anti-programmed death-1 (anti-PD-1) are associated with significant gastrointestinal (GI) toxicity such as diarrhea and colitis. We report a unique case of anti-PD1 induced lymphocytic colitis (LC). We also systematically review the current literature on this rare pathological entity. A systematic search of electronic databases was performed through August 2018 for all studies assessing diarrhea and colitis secondary to anti-CTLA4 and/or anti-PD1 use. Case-studies, case-series, and observational studies reporting immune-related microscopic colitis were included in the study. Case Report: 65F, with stage IV non-small cell lung cancer, was started on nivolumab therapy after progression on curative-intent chemoradiation therapy. Eight months later, despite disease improvement, she endorsed 4 watery bowel movements (BMs) per day without pain or blood. Nivolumab was held and a 2-week course of oral prednisone (1mg/kg) resulted in complete resolution of symptoms. Nivolumab was then re-started but she experienced an increase in BMs to 5–6/day. A 4-week taper of oral prednisone (1mg/kg) and nivolumab discontinuation resulted in complete diarrhea resolution. Nivolumab was re-started but her diarrhea relapsed, and she was admitted to the hospital with severe symptoms (35+ BMs/day with abdominal pain). Colonoscopy was unremarkable, but biopsies demonstrated an increase in lamina propria plasma cells and intra-epithelial lymphocytes consistent with LC. Intravenous methylprednisolone (1 mg/kg) was given with partial response. She was then prescribed one dose of infliximab 5mg/kg with immediate resolution of symptoms. Nivolumab was not restarted given the significant morbidity. Systematic Review: Seven studies were included: 4 case studies (8 patients) and 3 full-length manuscripts (11 patients). Seventeen patients were diagnosed with LC and 2 with collagenous colitis. Patient demographic and treatment data was available for 8 patients. Three patients were treated with pembrolizumab, 2 with nivolumab, 2 with atezolizumab, and 1 with ipilimumab. Two patients had a history of bladder cancer, and 1 each had a history of breast, renal, prostate, melanoma, lung, and anal cancer. Colonoscopy was normal in 6 patients and abnormal in 2 patients (mild left-sided congestion). Seven patients received high dose oral or intravenous methylprednisolone, only 3 achieved complete resolution. Three patients required infliximab therapy (2–4 doses) and one required vedolizumab therapy (2 doses) with complete resolution. Finally, one patient received budesonide (9mg/day) for 12 weeks with complete resolution of symptoms. Immune-related lymphocytic colitis appears to follow an aggressive course and may require biologic therapy such as anti-TNF agents. None

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