P0141 - Microbiome Alteration via Fecal Microbiota Transplantation (FMT) Is Effective for Immune Checkpoint Inhibitor (ICI) Induced-Colitis (IMC) Refractory to Immunosuppressive Therapy

Anusha Shirwaikar Thomas, MD¹, Taylor Halsey, MS¹, Zhi-Dong Jiang, MD, DrPh², Herbert DuPont, MD³, Robert Jenq, MD¹, Yinghong Wang, MD, PhD, MS^1
1University of Texas MD Anderson Cancer Center, Houston, TX; ²University of Texas Health Science Center at Houston, Houston, TX; ³University of Texas, Houston, TX

Introduction: Immune checkpoint inhibitors (ICI) target advanced malignancies with high efficacy, but also predispose to immune related adverse events such as immune-mediated colitis (IMC). While evidence-based management is lacking, medical therapy is limited to immunosuppressant therapy which may compromise cancer outcome. The composition of gut commensal bacteria is associated with response to ICI therapy and IMC severity, but optimal strategies to target the microbiome have yet to be identified. Fecal microbiota transplantation (FMT) represents a feasible way to restore microbial diversity and composition in patients for clinical benefit.

Methods: We present a case series of 12 patients with IMC who received FMT following unsuccessful treatment to immunosuppression with a detailed stool microbiome analysis. Of note, donor stool had successfully been employed previously in treatment of recurrent C.difficile diarrhea.

Results: All patients had advanced cancer with grade 3-4 diarrhea that failed immunosuppression. 3 patients received FMT twice. 83% had symptom improvement at a median duration of 14 days (IQR 9-16). Seven (58.3%) patients had complete clinical response, while five (41.7%) had either partial or no response. 42% of patients achieved both endoscopic and histologic remission at the last follow up. 4 (33%) resumed cancer therapy post FMT. 4 (33%) patients required immunosuppression for GI irAE after failing FMT. There were no FMT related complications at 7 and 30 days respectively. At the end of the study period, 92% achieved clinical remission. 3 patients in the cohort succumbed to underlying malignancy. The clinical characteristics are summarized in Table 1. 16S rRNA sequencing of patient stools before and following FMT revealed that complete response to FMT was significantly associated with greater gut dysbiosis before FMT, higher alpha diversity and an increased abundance in bacterial families Coriobacteriaceae and Bifidobacteriaceae from the phylum Actinobacteria post FMT. (Figure 1).

Discussion: FMT for refractory IMC represents a novel approach wherein the gut microbial diversity and composition may be targeted to confer therapeutic benefit for IMC. The data from this study gives greater insight into the unique microbial signatures that may play a role in FMT response to IMC. We speculate that routine use of FMT may have value in enhancing effectiveness of immunotherapy in some cancers while preventing gastrointestinal drug side effects




Disclosures:


Anusha Shirwaikar Thomas, MD¹, Taylor Halsey, MS¹, Zhi-Dong Jiang, MD, DrPh², Herbert DuPont, MD³, Robert Jenq, MD¹, Yinghong Wang, MD, PhD, MS¹. P0141 - Microbiome Alteration via Fecal Microbiota Transplantation (FMT) Is Effective for Immune Checkpoint Inhibitor (ICI) Induced-Colitis (IMC) Refractory to Immunosuppressive Therapy, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.