Zehn Skin and Health

A recent clinical trial has provided exciting new evidence that fecal microbiota transplantation (FMT) can improve the response to immunotherapy in patients with advanced melanoma. The study, published in Nature Medicine, involved 20 patients who received FMT from healthy donors before starting treatment with anti-PD-1 immunotherapy.  

What is FMT? Simply put, it is a medical procedure where stool from a healthy donor is transferred into the gut of a person who has an imbalance or poor diversity of gut bacteria. This helps restore a healthy gut microbiome. It’s commonly used to treat recurrent Clostridioides difficile (C. diff) infections and is being studied for other conditions like irritable bowel syndrome and inflammatory bowel disease. In this study, the stool was transferred from patients who had successfully responded to immunotherapy to those patients who no longer responded to cancer immunotherapy.

The researchers found that FMT was safe and well-tolerated, with no serious adverse events reported. Moreover, the combination of FMT and anti-PD-1 immunotherapy was associated with a 65% objective response rate, meaning that the tumors shrank or disappeared in two-thirds of the patients. This is significantly higher than the response rate typically seen with anti-PD-1 immunotherapy alone, which is around 40-45%.  

The researchers also investigated the mechanisms by which FMT might enhance the response to immunotherapy. They found that FMT led to changes in the composition of the gut microbiome, with an increase in the abundance of certain bacteria that have been associated with improved immune responses. They also observed changes in the patients’ immune systems, including an increase in the number of activated T cells, which are the cells that are responsible for killing cancer cells.  

These findings suggest that FMT may be a promising new strategy for improving the response to immunotherapy in melanoma patients. The researchers are now planning to conduct larger clinical trials to confirm these findings and to determine which patients are most likely to benefit from FMT.  

Reference:

• Routy, B., Lenehan, J.G., Miller Jr, W.H. et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. Nat Med 29, 2121–2132 (2023).