LONDON, ON – In a world-first clinical trial published in the journal Nature Medicine, a multi-centre study from Lawson Health Research Institute, the Centre hospitalier de l’Université de Montréal (CHUM) and the Jewish General Hospital (JGH) has found fecal microbiota transplants (FMT) from healthy donors are safe and show promise in improving response to immunotherapy in patients with advanced melanoma.
Immunotherapy drugs stimulate a person’s immune system to attack and destroy cancer. While they can significantly improve survival outcomes in those with melanoma, they are only effective in 40 to 50 per cent of patients. Preliminary research has suggested that the human microbiome – the diverse collection of microbes in our body – may play a role in whether or not a patient responds.
“In this study, we aimed to improve melanoma patients’ response to immunotherapy by improving the health of their microbiome through fecal transplants,” says Dr. John Lenehan, Medical Oncologist at London Health Sciences Centre’s (LHSC) London Regional Cancer Program (LRCP), Associate Scientist at Lawson and Associate Professor in the Department of Oncology at Western University’s Schulich School of Medicine & Dentistry.
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 connection between the microbiome, the immune system and cancer treatment is a growing field in science,” explains Dr. Saman Maleki, Scientist at Lawson and LHSC’s LRCP, Assistant Professor in Schulich Medicine’s Departments of Oncology, Pathology and Laboratory Medicine, and Medical Biophysics, and senior investigator on the study. “This study aimed to harness microbes to improve outcomes for patients with melanoma.”
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 per cent 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 CHUM’s Microbiome Center. “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.
This research is supported in part through donor funding from London Health Sciences Foundation, Western University, the Lotte and John Hecht Memorial Foundation, the JGH Foundation, Canadian Cancer Society’s Impact Grant program and The Terry Fox Foundation.
About Lawson Health Research Institute: Lawson Health Research Institute is one of Canada’s top hospital-based research institutes, tackling the most pressing challenges in health care. As the research institute of London Health Sciences Centre and St. Joseph’s Health Care London, our innovation happens where care is delivered. Lawson research teams are at the leading-edge of science with the goal of improving health and the delivery of care for patients. Working in partnership with Western University, our researchers are encouraged to pursue their curiosity, collaborate often and share their discoveries widely. Research conducted through Lawson makes a difference in the lives of patients, families and communities around the world. To learn more, visit www.lawsonresearch.ca.
About the CRCHUM: The CHUM Research Centre (CRCHUM) is one of North America’s leading hospital research centres. It strives to improve the health of adults through a continuum of research spanning disciplines such as basic science, clinical research and population health. More than 2,150 people work at the CRCHUM, including nearly 500 researchers and nearly 650 students and postdoctoral fellows. crchum.com
About the Jewish General Hospital: Part of the Integrated Health and Social Services University Network for West-Central Montreal (CIUSSS), the Jewish General Hospital has served patients from Montreal, elsewhere in Quebec, and beyond, since 1934. This McGill University teaching hospital, with approximately 600 beds, is one of the province's largest acute-care hospitals. It admits more than 22,000 patients per year, while handling approximately 578,000 outpatient visits, more than 84,000 emergency visits and more than 3,600 births. Treatment is provided by approximately 800 affiliated doctors, many of whom have teaching appointments at McGill University, as well as more than 300 medical residents per year, together with nursing and a wide range of allied health services.
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Method of Research
Randomized controlled/clinical trial
Subject of Research
Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial
Article Publication Date
B.R. reports grants from Kaleido, Vedanta, Surface and Da Volterra outside the submitted work, as well as consulting fees from BMS, AstraZeneca, Merck and Da Volterra. He is also the co-founder of Science Curebiota. B.H.M. has received consultancy fees from Finch Therapeutics Group and Ferring Pharmaceuticals, outside of the submitted work. R.J. reports grants from BMS, Merck and Iovance Biotherapeutics as well as consulting fees from BMS and Merck. M.K. is an employee at Pfizer. L.D. had consulting and advisory roles for BMS, Sanofi and EverImmune and was supported by the Philantropia Fondation Gustave Roussy. J.R.M. has received consultancies from Enterobiotix and Cultech outside of the submitted work. S.M.V. is a director of the board of IMV. The remaining authors declare no competing interests.