Fecal transplants show promise in improving melanoma treatment

Date:
July 7, 2023
Source:
Lawson Health Research Institute
Summary:
Researchers have found that fecal microbiota transplants (FMT)
from healthy donors are safe and show promise in improving response
to immunotherapy in patients with advanced melanoma.


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FULL STORY ==========================================================================
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'Universite' de Montre'al (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.

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========================================================================== Journal Reference:
1. Bertrand Routy, John G. Lenehan, Wilson H. Miller, Rahima Jamal,
Meriem
Messaoudene, Brendan A. Daisley, Cecilia Hes, Kait F. Al, Laura
Martinez- Gili, Michal Punčocha'ř, Scott Ernst, Diane
Logan, Karl Belanger, Khashayar Esfahani, Corentin Richard,
Marina Ninkov, Gianmarco Piccinno, Federica Armanini, Federica
Pinto, Mithunah Krishnamoorthy, Rene Figueredo, Pamela Thebault,
Panteleimon Takis, Jamie Magrill, LeeAnn Ramsay, Lisa Derosa,
Julian R. Marchesi, Seema Nair Parvathy, Arielle Elkrief, Ian
R. Watson, Rejean Lapointe, Nicola Segata, S.M. Mansour Haeryfar,
Benjamin H. Mullish, Michael S. Silverman, Jeremy P. Burton, Saman
Maleki Vareki. Fecal microbiota transplantation plus anti-PD-
1 immunotherapy in advanced melanoma: a phase I trial. Nature
Medicine, 2023; DOI: 10.1038/s41591-023-02453-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/07/230707111654.htm

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