Effect of fecal transplantation on patient reported outcomes after immune checkpoint inhibitor colitis.

Abstract

2517 Background: The use of fecal microbiota transplantation (FMT) has traditionally been reserved for the treatment of recurrent Clostridioides difficile infections (CDI). As the gut microbiome has been increasingly acknowledged to play a role in a variety of bodily processes, FMT has seen its application extended to other gastrointestinal disorders. Immune-mediated colitis (IMC) is a similar entity to inflammatory bowel disease and arises as a side effect of immune checkpoint inhibitor therapy to stimulate the immune response. Treatment of IMC is mostly limited to immunosuppressants e.g. corticosteroids, infliximab, and vedolizumab. Cases refractory to such medications pose a significant challenge. FMT has been shown to be a successful treatment in refractory IMC in small case series, further large studies are needed to determine its efficacy. Methods: We measured the efficacy of FMT for refractory IMC among 37 patients via chart review and clinical assessment and patients’ reported outcome (PRO) via established MD Anderson Symptom Inventory (MDASI). Among them, 9 patients had concurrent CDI as well at the time of diagnosis. Results: Fifty-nine patients were included in our study. Most patients had a peak diarrhea grade ≥ 3 (94.9%) and colitis grade ≥ 2 (91.5%). Ulcerous (26, 44.1%) and non-ulcerous (21, 35.6%) inflammation were the predominant endoscopic findings. Fifty-seven (96.6%) patients received corticosteroids, and 54 patients (91.5%) received add-on infliximab or vedolizumab. IMC symptom response was 84.7% after FMT with median time to response of 4 days. The transient complication rate is 30.5% at 7 days and 18.6% at 30 days. Response rate among the 50 patients without concurrent CDI was 86.0%. Fifty (84.7%) patients demonstrated clinical remission by the end of the study period, and 11 (18.6%) were able to resume ICI treatment, and among them, 9 patients remained in remission. A total of 10 patients (16.9%) in our cohort developed recurrent colitis after FMT requiring immunosuppression; 3 of these recurrent cases were triggered by ICI resumption. On the PRO analysis, we observed a favorable trend of significant patient-reported symptom reduction on diarrhea (61% to 11%, p<0.01) and abdominal bloating (36% to 7%, p<0.05) during 12 weeks after FMT. There was a 49.4% reduction of moderate to severe symptoms with only 44% of patients reporting such symptoms after 12 weeks (down from 89%, p<0.01). Conclusions: FMT may serve as a potential treatment option in IMC refractory to standard treatment to avoid long-term steroid dependency and immunosuppression. It is effective to maintain IMC remission with a low complication rate. The role of the gut microbiome in cancer and the implications for FMT remain uncertain and need further elucidation. Clinical trial information: NCT03819296 .