Fecal Transplants Show Promise in Improving Response to Immunotherapy in Melanoma Patients

Combining fecal transplants with immunotherapy is safe for patients, and the study also found 65% of patients who retained the donors’ microbiome had a clinical response to the combination treatment.

Fecal microbiota transplants (FMT) from healthy donors are safe and show promise in improving response to immunotherapy in patients with advanced melanoma, according to research in Nature Medicine.

Preliminary research has suggested that the human microbiome may play a role in whether or not a patient responds to immunotherapy.

A fecal transplant involves collecting stool from a healthy donor, screening and preparing it in a lab, and transplanting it to the patient. The goal is to transplant the donor’s microbiome so that healthy bacteria will prosper in the patient’s gut.

The phase I trial included 20 melanoma patients recruited from LHSC, CHUM and Jewish General Hospital. Patients were administered approximately 40 fecal transplant capsules orally during a single session, one week before they started immunotherapy treatment.

The study found that combining fecal transplants with immunotherapy is safe for patients – which is the primary objective of a phase I trial (also called ‘safety trials’). The study also found 65% of patients who retained the donors’ microbiome had a clinical response to the combination treatment. Five patients experienced adverse events sometimes associated with immunotherapy and had their treatment discontinued.

“We have reached a plateau in treating melanoma with immunotherapy, but the microbiome has the potential to be a paradigm shift,” says Dr. Bertrand Routy, Oncologist and Director of Centre hospitalier de l’Université de Montréal’s (CHUM) Microbiome Center, in a news release.

“This study puts Canada at the forefront of microbiome research by showing we can safely improve patients’ response to immunotherapy through fecal transplants.”

“These exciting results add to a rapidly growing list of publications suggesting that targeting the microbiome may provide a major advance in the use of immunotherapy for our patients with cancer,” adds Dr. Wilson H. Miller Jr. of the JGH and Professor in the Departments of Medicine and Oncology at McGill University.

The study is unique due to its administration of fecal transplants (from healthy donors) in capsule form to cancer patients – a technique pioneered in London by Dr. Michael Silverman, Lawson Scientist, Chair of Infectious Diseases at Schulich Medicine and Medical Director of the Infectious Disease Care Program at St. Joseph’s Health Care London.

“Our group has been doing fecal transplants for 20 years, initially finding success treating C. difficile infections. This has enabled us to refine our methods and provide an exceptionally high rate of the donor microbes surviving in the recipient’s gut with just a single dose,” says Dr. Silverman. “Our data suggests at least some of the success we are seeing in melanoma patients is related to the efficacy of the capsules."

The team has already started a larger phase II trial involving centres in Ontario and Quebec. Lawson researchers are also studying the potential of fecal transplants in the treatment of other cancers, including renal cell carcinoma, pancreatic cancer and lung cancer, as well as HIV and rheumatoid arthritis.

PHOTO IMAGE: DR. SAMAN MALEKI AND DR. JOHN LENEHAN DISCUSS THE RESULTS OF THEIR RECENT STUDY ON FECAL TRANSPLANTS FOR ADVANCED MELANOMA PATIENTS. view more 

PHOTO CREDIT: LAWSON HEALTH RESEARCH INSTITUTE