Halsey and Thomas et al. retrospectively studied 12 ICI-treated patients with various cancers who received fecal microbiota transplants (FMT) from healthy donors to treat grade 3 or 4 ICI-related refractory immune mediated colitis (IMC). Ten patients’ symptoms improved after FMT, including 3 complete responses. Three partial responders repeated FMT; one responded. At study’s end, 92% had IMC remission. There were no FMT-related complications. Complete response was associated with differences in donor and recipient pre-FMT fecal microbiome composition, increases in alpha diversity and levels of Collinsella and Bifidobacterium, which were low in responders’ baseline stool samples, and decreases in colonic CD8+ T cells.
Contributed by Paula Hochman
ABSTRACT: Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium, which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells , including CD8(+) T cells, in the colon after FMT when compared with non-complete response patients (n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.
Author Info: (1) Graduate School of Biomedical Sciences, Microbiology and Infectious Diseases, University of Texas MD Anderson Cancer Center UTHealth Houston, Houston, TX 77054, USA. (2) Depart
Author Info: (1) Graduate School of Biomedical Sciences, Microbiology and Infectious Diseases, University of Texas MD Anderson Cancer Center UTHealth Houston, Houston, TX 77054, USA. (2) Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (3) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (4) Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province 430071, People's Republic of China. (5) Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Department of Internal Medicine, University of Missouri, Kansas City, MO 65211, USA. (6) Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (7) Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (8) Center for Infectious Diseases, School of Public Health, University of Texas, Houston, TX 77054, USA. (9) Center for Infectious Diseases, School of Public Health, University of Texas, Houston, TX 77054, USA. Kelsey Research Foundation, Houston, TX 77005, USA. (10) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (11) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (12) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (13) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (14) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (15) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (16) Middlebury College, Middlebury, VT 05753, USA. (17) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (18) Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (19) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (20) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (21) Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Department of Stem Cell Transplantation, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. (22) Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
