Researchers at The University of Texas MD Anderson Cancer Center report that, for the first time, the transplantation of gut bacteria from healthy donors was used to successfully treat patients suffering from severe colitis caused by treatment with immune checkpoint inhibitors (ICIs).
While ICIs have successfully provided durable responses for a subset of patients across a number of different cancer types, the treatments, which release a block on the immune system to attack cancer, are often associated with significant immune-related toxicities. Colitis is the second most common side effect of ICIs affecting as many as 40 percent of patients receiving these treatments. The research suggests that fecal microbiota transplantation (FMT) is worth investigating in clinical trials as a therapy for this common side effect.
The research, led by Yinghong Wang, M.D., Ph.D., assistant professor of Gastroenterology, Hepatology & Nutrition and director of Medication Induced Colitis and Enteritis, was published Nature Medicine.
“The resolution of colitis in these patients can be confirmed clinically and endoscopically after FMT treatment,” said Wang in a press release announcing the study’s findings. “Based on these results, this should be evaluated even as a first-line therapy for ICI-associated colitis because it’s safe, quick, and the effect is durable - from one treatment.”
Finding an effective way to treat colitis during immunotherapy is important as current guidelines call for the discontinuance of providing ICIs to patient with severe ICI-related colitis until it is in remission.
“If the patient is a good responder to immunotherapy, that means you’ve taken their effective treatment away,” said Wang. “We have a limited amount of time to fix the problem so they can resume ICI treatment, but I feel that we’ve made great progress in this area.”
FMT has been under investigation for a range of gastrointestinal diseases, such as recurrent Clostridium difficile infection and inflammatory bowel disease (IBD) and has shown promise for treating these conditions, as well. Both share many clinical and molecular characteristics with ICI-associated colitis.
The recent study was limited to two patients, both of whom had complete resolution to the colitis after receiving FMT treatment. One patient’s colitis resolved within two weeks of receiving the FMT, while the second patient had a partial recovery after the first treatment, then fully recovered after receiving a subsequent treatment.
Post treatment stool analyses of the patients’ gut microbiomes revealed they were more similar to the donor’s microbiome directly after treatment than their pre-treatment microbiome. Yet, each patient’s microbiome resembled the donor’s less over time. Significantly, there were distinct new populations of bacteria evident in these patients following FMT compared to pre-treatment samples, including several species known to be protective or reduce inflammation.
With a cohort of only two patients the MD Anderson team understand the significant limitations of their study, though the result were encouraging enough for them to plan clinical trials to study the effectiveness of FMT treatments for ICI-induced colitis.