Could fecal transplants improve melanoma treatment?

Evan Walker
Evan Walker TheMediTary.Com |
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Fecal transplants could be used in conjunction with current cancer treatments to boost results. /Getty Images THIERRY ZOCCOLAN/Getty Images
  • Combining fecal transplants with immune checkpoint inhibitors such as pembrolizumab or nivolumab showed the procedure was safe in people with advanced melanoma, according to a phase 1 clinical trial.
  • Of the study participants, 65% responded positively to immunotherapy treatment.
  • Positive responders also showed an increase in beneficial bacteria and a decrease in harmful bacteria in their gut microbiome following the fecal transplant.
  • The researchers plan to conduct larger phase 2 trials and explore using fecal transplants in hard-to-treat cancers like pancreatic cancer.

In recent years, a type of treatment called immunotherapy has been helping many people with cancer by harnessing their immune systems to recognize and destroy cancer cells.

Some drugs used in immunotherapy, like pembrolizumab (Keytruda) and nivolumab (Opdivo), work by stopping the mechanism that allows cancer cells to hide from the immune system.

These ‘anti-programmed death (PD-1) drugs’ or ‘immune checkpoint inhibitors’ are effective in treating nearly 50% of people with melanoma (a type of skin cancer).

Recently, scientists tested combining immunotherapy with fecal microbiota transplants in patients with advanced melanoma to see whether this could improve their response.

Not only was this combination safe, but most patients also saw a positive response to the treatment, with some achieving complete remission.

The study is published in Nature Medicine.

All 20 patients were able to complete the fecal transplantation procedure.

Eight patients (40%) experienced mild to moderate side effects related to fecal transplantation, including diarrhea, flatulence, and abdominal discomfort, but no serious side effects were observed before starting immunotherapy, and no infections were transmitted through fecal transplantation.

Of the patients, 17 people (85%) experienced immune-related side effects, most of which (70%) occurred within the first three months after starting immunotherapy. Of these, five study participants (25%) had severe immune-related side effects, including arthritis (n = 2), fatigue (n = 1), pneumonitis (n = 1), and nephritis (n = 1), which led to treatment discontinuation.

The researchers did not observe any previously unreported side effects of fecal transplantation or immunotherapy.

Dr. John Lenehan, medical oncologist at London Regional Cancer Program, associate scientist at Lawson Health Research Institute, associate professor of oncology and family medicine at Western University, and principal study investigator, told Medical News Today the most important finding in this study, for him, was that “none of the patients were harmed by the experimental treatment.”

Observational and pre-clinical data had shown fecal transplants to be helpful, “but what happens in mice does not always translate to patients,” he said. Indeed, Dr. Lenehan noted that “more recent studies using similar therapies have shown harm, with patients having a worse response.”

He explained that these other studies performed fecal transplantation differently from the MIMic trial.

“There are many variables such as bowel preparation, how many FMTs need to be done, how much stool is needed, who should the donors be? We did not know if our method would be safe or effective. Fortunately, it seems that it was both!” he said.

Hannah Wardill, Ph.D., research fellow at the Hospital Research Foundation Group and leader of the Supportive Oncology Research Group at the University of Adelaide, who was not involved in this study, believes that this combination therapy approach has the potential to become a successful treatment.

“FMT is a reasonably accessible intervention, and this study shows it is safe and likely effective and improving immunotherapy response,” she told MNT.

By enhancing response rate in people who would otherwise be unresponsive to immunotherapy, the combination of fecal transplants and immunotherapy means that “more people will benefit from immunotherapy,” Dr. Wardill explained.

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