Prophylactic vedolizumab to facilitate use of immune-checkpoint inhibitors in cancer patients at high risk of immune-mediated colitis.

12134 Background: Inflammatory diarrhea/colitis is a frequent immune-related adverse event (IRAE) associated with immune checkpoint inhibitors (ICIs). Treatment with ICI is relatively contraindicated in patients with history of severe ICI-colitis or those with pre-existing severe inflammatory bowel diseases (IBD). Vedolizumab (VDZ), an anti-α4β7 integrin antibody associated with selective immune suppression in the gastrointestinal (GI) tract, is approved for IBD treatment and is also effective in treating steroid-refractory ICI-colitis. However, limited data exist for its utility as a prophylactic treatment for primary or secondary prevention of ICI-colitis in high-risk patients. Methods: We conducted a single-center, retrospective study of patients with advanced skin cancers, who were deemed “high-risk” due to prior severe ICI colitis or IBD, and received VDZ prophylaxis prior to ICI (re)treatment. VDZ efficacy was assessed by analyzing the frequency, severity, duration and treatment details of GI symptoms. In patients with prior ICI-colitis, outcomes with and without VDZ prophylaxis were compared using descriptive statistics. ICI efficacy in the presence of VDZ was evaluated by objective response rate (ORR) per RECIST v1.1. Results: We identified 16 high-risk patients (11- prior ICI colitis, 5 – IBD) who received VDZ prophylaxis (typically 300 mg at weeks 0, 2, and 6 initially, then q8 weeks) prior to ICI (re)treatment, between 2015-2025. Median number of VDZ doses before (re)introducing ICI was 2 (range, 1-3). In the ICI-colitis cohort, VDZ prophylaxis prior to ICI re-treatment resulted in less frequent and milder GI symptoms not needing corticosteroids, than previously observed with initial ICI treatment without VDZ prophylaxis (see Table). Among 14 patients with evaluable disease (measurable and progressing at the time of VDZ treatment), ORR was 33% (3/9) in the ICI-colitis cohort and 80% (4/5) in the IBD cohort. Conclusions: Use of prophylactic VDZ can facilitate successful, long-term ICI treatment in high-risk patients with prior ICI-colitis or IBD, while mitigating GI symptoms, reducing corticosteroid usage and preserving anti-tumor responses. ICI-colitis cohort, without VDZ prophylaxis (N = 11) ICI-colitis cohort, with VDZ prophylaxis (N = 11) IBD cohort, with VDZ prophylaxis (N = 5) Diarrhea (any grade), n (%) 11 (100) 3 (27) 4 Diarrhea (≥ grade 3), n (%) 8 (73) 0 2 (40) Symptom duration in days, Median (range) 75 (13, 251) 46 (8, 54) 39 (17, 129) Corticosteroid use, n (%) 11 (100) 0 2 (40) Corticosteroid use in days, Median (range) 54 (7, 102) N/A 59 (59, 59) Additional biologic therapy, n (%) 10 (91) 0 3 (60) ICI discontinuation due to diarrhea, n (%) 11 (100) 2 (18) 3 (60) ICI treatment duration in months, Median (range) 2.1 (1.4, 17.5) 7.7 (1.1, 49.0)* 7.4 (6.7, 20.8) *4 patients had ongoing ICI treatment.