A109 CHECKPOINT INHIBITOR-RELATED LYMPHOCYTIC COLITIS: A NEW, PATHOLOGICAL ENTITY
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Bibliographic record
Abstract
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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it