Potential of Fecal Microbiota Transplantation in Managing Immunotherapy-Associated Colitis
Immune checkpoint inhibitors are associated with potentially serious IRAEs, such as immune-mediated colon inflammation, or colitis.
Fecal bacteria appear to play important roles in colon inflammation (colitis) and tumor biology. A pair of case studies suggest that healthy-donor fecal microbiota transplantation (FMT) can resolve anticancer immune checkpoint inhibitor (ICI)-induced colitis. However, ICI colitis has clinical and histopathologic mimics and should be carefully differentiated from other colitis etiologies.
The 2 patients' treatment-resistant ICI-associated colitis went into remission soon after endoscopic FMT, which was offered on a compassionate-use basis.1
“The resolution of colitis in these patients can be confirmed clinically and endoscopically after FMT,” explained lead study author Yinhong Wang, MD, PhD, MS, of the Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, in Houston, Texas. “Based on these encouraging results, this should be evaluated even as a first-line therapy for ICI-associated colitis because it is safe, quick, and the effect is durable, from one treatment.”
The findings suggest that earlier work on mouse models can be successfully translated to clinical benefits for human patients, Dr Wang told Oncology Nurse Advisor.
Immune checkpoint inhibitors counteract some tumors' ability to slow antitumor immune response using the checkpoint mechanism through PD1 and CTLA4, offering sometimes dramatic tumor responses for a minority of patients. But these agents are also associated with potentially serious immune-related adverse events (IRAEs) such as immune-mediated colon inflammation, or colitis. Severe ICI-associated colitis can lead to significant morbidity and a halt in ICI therapy until colitis is successfully resolved. The development of treatment options for patients with immunosuppression (eg, corticosteroid)-refractory ICI colitis is therefore an urgently important task.
Patients who benefit from ICIs but who experience IRAEs are being denied an effective, potentially life-prolonging treatment when that treatment is interrupted or discontinued. “We have a limited amount of time to fix the problem so they can resume ICI treatment,” explained Dr Wang.
Corticosteroid therapy can also diminish the efficacy of ICIs, and immunosuppressive treatment usually causes other comorbidities, such as Clostridium difficile infections, so first-line treatment of ICI colitis with FMT instead of steroids should be explored.
Donor fecal bacterial ecologies appear to remain fairly stable in recipients' guts but over time they do evolve.
“There are a number of factors that could be involved in this process,” Dr Wang explained. “One is if a patient had to be exposed to antibiotics afterwards. Because sicker patients tend to get infections, they get antibiotics and that can potentially change their microbiome. Second, other cancer treatments have the potential to also affect the microbiome pattern. So, with time, microbiomes start to change from the initial [donor] combination of bacterial species.”
“Surprisingly, even though their microbiome patterns shifted away from donor [ecologies] a little bit after a few months, our patients' clinical symptoms remained very stable,” she noted. “They don't have recurring symptoms. We found that a little surprising.”
However, when donated fecal ecologies change, Dr Wang added, it would “not be a big deal to perform another fecal transplant, if needed.”
Previous preclinical research has suggested that feeding fecal bacteria to mice with immune checkpoint inhibition might offer a synergistic effect on tumor regression.
“That suggests certain gut bacteria species can play a big role in tumor regression,” she said.