P93 Faecal microbiota transplant for refractory checkpoint inhibitor immunotherapy-related colitis

Introduction Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of various cancers. They improve survival but this comes at the cost of immune-related adverse events like ICI-colitis. First line treatment is steroids and refractory cases can be treated with infliximab, vedolizumab or faecal microbiota transplant (FMT). We describe our experience of FMT, alongside cytometric/transcriptomic analysis of the GI immune response, and whole stool metabolomic analysis pre- and post-FMT. Methods 150 ml FMT was delivered to the caecum by colonoscopy. 5 pairs of colon pinch biopsies were collected pre- and week 6 post-FMT. Gut mononuclear cells (GMNC) were isolated from the biopsies by enzymatic/mechanical digestion. GMNC were analysed using a 21-parameter flow cytometry panel on the Cytek Aurora Spectral Analyser and a 780-plex Nanostring panel. Stool pre- and post-FMT, and that of the FMT donor, was subjected to whole metabolome analysis. Results Two patients with refractory ICI-colitis were treated with FMT (same donor). Characteristics are shown in Table 1: Patient 1’s symptoms of diarrhoea and abdominal pain resolved fully. Week 6 sigmoidoscopy and biopsies were normal. Pre-FMT, there were high levels of activation (as measured by co-expression of HLA-DR and CD38) on CD4, CD8 and MAIT cell subsets as well as high Ki-67 and low expression of Bcl-2. Post FMT, there was reduced expression of HLA-DR and CD38 and lower expression of Ki-67 with high/homeostatic levels of Bcl-2 and an increased proportion of Tregs. The bowel frequency of patient 2 demonstrated some clinical improvement, but week 6 sigmoidoscopy showed an unchanged UCEIS score and Nancy histological index. Pre FMT, there were similar levels of activation as seen in patient 1, but post-FMT responses were muted. We will present an analysis of the GI immune response and of the stool whole metabolome, in these two patients with dichotomous clinical outcomes. Conclusions We report the first use of FMT to treat ICI-colitis in the UK, demonstrating that it is effective in a subset of patients. Although both patients received stool from the same donor, they experienced contrasting treatment responses. We will present the salient GI immune and stool metabolomic differences to reveal mechanistic insights.