Fecal transplant may improve response to immunotherapy among patients with melanoma

Fecal microbiota transplant from healthy donors may lower primary resistance to immunotherapy with anti-PD-1 agents among patients with advanced or metastatic melanoma, results of the phase 1 MIMic trial showed.

Three-quarters of patients in the study experienced some type of clinical benefit from the combination strategy, according to findings presented during Society for Immunotherapy of Cancer Annual Meeting.

Background

Composition of a patient’s gut microbiome has previously been shown to influence response to immunotherapy, according to Saman Maleki, PhD, assistant professor in the departments of oncology, pathology and laboratory medicine, and medical biophysics at Western University.

“Multiple studies have shown that there are several bacteria that can be found in patients who respond to immune checkpoint inhibitors,” he said during a presentation. “Patients who do not respond to immune checkpoint inhibitors have their own signature of bacteria, as well.”

Previous studies used patients already exposed to therapy with immune checkpoint inhibitors, Maleki noted.

"With this in mind, we decided to test the ability of the gut microbiome to impact the response to immunotherapy in the anti-PD-1-naive setting,” he said.

Methodology

The MIMic trial treated 20 patients (median age, 75.5 years) with unresectable or metastatic cutaneous melanoma who had not received previous anti-PD-1 therapy.

Study participants received a fecal microbiota transplant via capsules from one of three healthy donors 1 week before starting standard-of-care therapy with an anti-PD-1 agent at one of three hospitals in Canada.

Safety served as the study’s primary endpoint. Median follow-up was 12.2 months.

Key findings

No grade 3 or grade 4 adverse events attributed to fecal microbiota transplant occurred during the study. Five patients experienced grade 3 immune-related adverse events, including two patients with arthritis and one patient each with fatigue, pneumonitis and nephritis.

Investigators reported a response to therapy in 13 of 20 patients (65%), including three patients with a complete response.

Fifteen patients (75%) had a reported clinical benefit of at least stable disease lasting 6 months or longer from the combination of fecal microbiota transplant and anti-PD-1 therapy.

All patients, regardless of response to therapy, demonstrated increased microbiome diversity after transplant, Maleki noted.

“However, only treatment responders managed to maintain their donor’s microbiome over time,” he added.

Clinical implications

Evidence from the study suggests that successful donor microbiome engraftment and retention is linked to response to immunotherapy, Maleki noted.

“The combination of healthy donor fecal microbiota transplant with anti-PD-1 therapy is safe as first-line therapy in patients with melanoma,” he told the audience. “Donor microbiome engraftment can induce a response to anti-PD-1 therapy and potentially reduce primary resistance to immunotherapy.”

Further study in this area is planned, including the use of repeated fecal transplant in patients who do not maintain donor microbiomes after their initial transplant, Maleki said.

In addition, a randomized phase 3 study is needed to determine the overall impact of fecal transplant on immunotherapy outcomes.

“Microbiome modification through fecal microbiota transplant has the potential to dramatically impact patients’ response to immunotherapy,” Maleki told Healio.