A233 VEDOLIZUMAB FOR STEROID & INFLIXIMAB-REFRACTORY ICI-COLITIS
Bibliographic record
Abstract
Abstract Background Immune checkpoint inhibitors (ICI), such as anti-PD1, improve survival in melanoma, renal carcinoma and prostate cancer. However, by disinhibiting the immune system, these treatments cause significant immune-related adverse events (irAE), including colitis. For ICI-colitis, guidelines suggest escalating from observation to steroids to infliximab, without strong evidence for additional options should these fail. Vedolizumab has been used in a small number of cases for steroid-refractory or dependent ICI-colitis; only 9 cases have been reported in patients who failed infliximab therapy with a response rate of 67%. Aims To discuss a case of ICI-colitis that failed multiple steroid courses and infliximab infusions, but achieved remission with vedolizumab. Methods A 65-year-old male with malignant melanoma was randomized to adjuvant nivolumab +/- ipilimumab and developed non-bloody diarrhea. Despite loperamide, diarrhea worsened to 4–5 bowel movements daily. Stool cultures and C. diff were negative and 85mg of daily prednisone was started, while the ICI was held for 8 weeks. After a 2nd steroid taper, diarrhea recurred and the patient received 2 infliximab infusions 18 days apart. Despite initial improvement, biopsies demonstrated colitis and he underwent a 3rd infusion with little response. Clinical and biopsy-confirmed remission was only achieved once 2 vedolizumab infusions were given. Results Colitis is the most common ICI irAE, ranging in severity from mild to perforation and death. The incidence of grade 3 and 4 colitis, which require ICI discontinuation, is 1.3% for anti-PD1 and 13.6% in combination therapy. The severity of irAE is positively correlated with malignancy response and stopping ICI risks recurrence. Those that fail irAE medical management may require surgery. Thus, there is an impetus to continue the ICI and provide effective medical management for irAE. ICI-colitis guidelines are based on the CTCAE diarrhea classification and suggest supportive management and ICI continuation for grade 1. For grade 2, the ICI is held and steroids are started; infliximab is added for grades 3 and 4. However, 33–66% of patients are steroid-refractory or dependent; and patients may be infliximab non-responders, or unable to tolerate systemic side effects. Vedolizumab, an anti-α4β7-integrin, acts locally to inhibit T cells in the bowel wall, reducing inflammation in IBD. Recent reports, including ours, suggest usefulness in steroid and infliximab-refractory ICI colitis after only 2–4 infusions. When the inflammatory burden is high, the response rate is >80% and given its gut-specificity, side effects are minimal compared to infliximab. Although further evaluation is required, using vedolizumab as second-line therapy is reasonable. Conclusions Given vedolizumab’s safety and gut-specificity, it should readily be considered in the treatment of ICI irAE. Funding Agencies None
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".