TOPLINE

A phase 1/2 clinical trial found that first-line fecal microbiota transplantation (FMT) achieved clinical response in 10 of 13 patients with cancer who developed immune checkpoint inhibitor-mediated diarrhea and colitis (IMDC), with symptoms improving in a median of just 1.5 days. The approach could offer a faster, steroid-sparing alternative for managing this common and often treatment-limiting side effect of cancer immunotherapy. 

METHODOLOGY

• Immunotherapy-related diarrhea and colitis can force patients to pause cancer treatment, with steroids and biologics typically used for management. FMT restores healthy gut bacteria from a screened donor, but its effectiveness as a first-line treatment had remained largely unexplored.
• Researchers conducted a phase 1/2 clinical trial to evaluate the efficacy and safety of first-line FMT in 13 patients (median age, 65 years; 53.8% men) who developed grade ≥ 2 IMDC after cancer immunotherapy between June 2021 and April 2024 at a single center in the US; 84.6% had genitourinary cancer, and 76.9% had stage IV cancer.
• Patients received FMT through colonoscopy, with 50 grams of donor stool delivered to the right side of the colon at a median of 26 days after IMDC onset; they were tracked closely after the procedure: checked daily during week 1, weekly through the first month, then monthly for 3 months, with repeat scopes at the 4-, 8-, or 12-week mark and a safety review at 6 months.
• Samples of stool, blood, and colon tissue were analyzed throughout to track shifts in gut microbes, metabolic byproducts, immune cell activity, and circulating inflammatory signals.
• The primary outcomes were clinical response or remission within 2 weeks of FMT, and FMT-related adverse events during the first 3 months. 

TAKEAWAY

• Clinical response was achieved in 76.9% of the patients, with improvement in symptoms seen within a median of 1.5 days after the treatment; among those initial responders, 80% maintained sustained remission through the median 6.5-month follow-up. 
• FMT-related adverse events were observed in 23.0% of patients, including transient fever, gassiness, nausea, and abdominal pain. All events were grade 1 and resolved with conservative management.
• Endoscopic remission occurred in 33.3% of patients with baseline gross inflammation, and histologic remission in 18.1% of those with baseline inflammation on biopsy. Median fecal calprotectin improved from 416 mcg/g to 146 mcg/g. Most patients (11 of 13) were able to resume some form of cancer treatment after their gut symptoms resolved, and 5 went back on immunotherapy itself.
• Among 8 responders whose stool was sequenced, 6 (75%) showed increased microbial diversity after FMT, alongside a shift toward a more donor-like profile with gains in bacteria such as, Alistipes shahii and Lacrimispora amygdalina. 

IN PRACTICE

"What stands out in these results is the quick onset of clinical improvement from an early introduction of microbiome therapy as well as the number of patients who were able to resume cancer treatment," said the lead author in a press release. "These findings suggest FMT may have a role earlier in the course of immunotherapy-related colitis as a quick and effective treatment that could mitigate the exposure to immunosuppressive treatment as well as related complications."

SOURCE

The study was led by Yinghong Wang, MD, The University of Texas MD Anderson Cancer Center, Houston. It was published online in Cell Reports Medicine.

LIMITATIONS

A small number of patients at a single center were enrolled in the study,  limiting the generalizability of the findings. Most participants had advanced-stage disease and represented a limited range of cancer types, which restricted broader applicability of the result. The study lacked a control group, so the improvement could not be attributed to FMT with certainty.

DISCLOSURES

One author received funding from the Adopt-A-Scientist grant, The University of Texas MD Anderson Cancer Center Faculty start-up fund, and The University of Texas MD Anderson Cancer Center Division of Internal Medicine IOTOX research award. Another author disclosed receiving patent royalties and serves as a senior advisory board member for industry.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.