B0423 - Favorable Colitis Outcome After Combination Therapy With Gut Selective Anti-Integrin and Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor Diarrhea and Colitis

Ninoska N. Silva, MPAS, PA-C, Yinghong Wang, MD, PhD, Anusha S. Thomas, MD
MD Anderson Cancer Center, Houston, TX

Introduction: Immune-checkpoint inhibitor (IMC) diarrhea/colitis, is the most common immune-related adverse events (irAEs) often leading to delay/ interruption in cancer care. Initial work-up includes ruling out infectious etiology of diarrhea/colitis. Medical therapy of IMC is limited to immunosuppressant therapy. Anti-integrin therapy, namely vedolizumab selectively inhibits the influx of inflammatory cells into the bowel and bears a favorable safety profile in cancer patients. Additionally, the composition of gut commensal bacteria is associated with both response to immune checkpoint inhibitor (ICI) therapy and IMC severity. Fecal microbiota transplant (FMT) has demonstrated utility in management of recurrent Clostridium difficile infection as well as IMC patients. We present a case series of two patients with advanced malignancies who developed IMC and were successfully treated with anti-integrin therapy and FMT.

Case Description/Methods: Case 1: A 64-year-old Caucasian woman with metastatic cervical cancer on pembrolizumab developed Common Terminology Criteria for Adverse Events (CTCAE) grade 3 diarrhea. Infectious work-up was positive for C. difficile. Colonoscopy demonstrated moderate pancolitis with biopsies showing chronic active colitis. She underwent FMT followed by vedolizumab therapy and is currently in clinical remission.

Case 2: A 77-year-old Caucasian woman with metastatic urothelial cancer on pembrolizumab presented with grade 2 diarrhea. Infectious work-up was negative. Endoscopic evaluation was notable for normal-appearing small and large bowel mucosa with histology demonstrating lymphocytic colitis. She received vedolizumab followed by FMT and remains in clinical remission.

Discussion: The microbial composition within the GI tract should be at the forefront of considerations in management of ICI colitis. Fecal microbiota transplant for the treatment of IMC represents a novel approach to manipulate the gut microbiome of IMC patients and confer clinical benefit. Vedolizumab is an anti-integrin α4β7 antibody with gut-specific immunosuppressive effects that has demonstrated success in the management of IMC without interfering with ICI therapy. Studies looking into the synergistic effect of gut selective immunosuppression with therapeutic manipulation of the gut microbiome need to be considered.




Disclosures:


Ninoska N. Silva, MPAS, PA-C, Yinghong Wang, MD, PhD, Anusha S. Thomas, MD. B0423 - Favorable Colitis Outcome After Combination Therapy With Gut Selective Anti-Integrin and Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor Diarrhea and Colitis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.