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Fecal transplants show promise in improving melanoma treatment
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 JGH. 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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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.
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.
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Lawson Health Research Institute
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International Women's Day 2020
International Women’s Day, taking place on March 8, 2020, is a day to celebrate the various achievements of women around the world and is a call to action for gender parity. This year’s theme is “Each for Equal” to emphasize that each individual has a significant part in working towards a gender equal world.
This year, Lawson is highlighting the different paths for women who are working towards a career in the health sciences. Below are the perspectives from students, physicians and researchers on their contributions to science and medicine.
High school student, Nimrit Aulakh, is completing her co-op placement with Lawson Scientist, Dr. Cheryl Forchuk. Her research focuses on improving mental health care for youth.
“Science has always been of interest to me and has now become significant within my academic endeavours. Part of my desire to become involved in the sciences stemmed from my older sister, who exposed me initially to the research side of science. It is with the help of rationale and logic in science that I can enrich my academic experience. Specifically, I have been working as a co-op student alongside the Mental Health Nursing Research Alliance and learning what it means to be a researcher. During my time, I conducted preliminary analyses on one of their studies, which focuses on improving mental health care for youth through virtual models of care. I will be presenting my findings at the Thames Valley Science and Engineering Fair later this month and if successful, will advance to the Canada Wide Science Fair. This experience has shown me a new side of science, one that I hope that I can continue to be a part of. I realized that through science and research, I can contribute to advancing society. To continue my journey through post-secondary education, I have applied to get my Bachelor’s in Health Sciences. Both within and beyond my four years of undergraduate studies, I hope to continue my contributions in serving the public through scientific research, as well as create an image for girls with the same interests as me, everywhere.”
Romaisa Pervez is a Research Assistant working with Lawson Scientist, Dr. Arlene MacDougall. She recently completed her Master of Science in Epidemiology and Biostatistics at Western University.
“I’m the student lead on a project that’s titled “Building a Sustainable Model and Evaluation for Psychological Rehabilitation in Kenya: An Implementation Study.” I’m working with the CREATE (Community Recovery Achieved Through Entrepreneurism) Kenya team to conduct a study to improve how we deliver, evaluate, and train persons with lived experience or community members to facilitate the Psychosocial Rehabilitation (PSR) Toolkit so it can be locally sustained in Kenya. I’ve travelled to Kenya twice during my Master’s to build relationships with stakeholders and conduct focus groups/interviews. My passion lies in understanding how we can implement upstream initiatives for mental health that are both sustainable and effective. Furthermore, I want to explore how we can find leverage points within the current mental health system in low to middle income countries and create innovative solutions. In the near future, I want to pursue medicine and further my knowledge and build stronger skills in this field.”
Dr. Kelly Anderson is an Associate Scientist at Children’s Health Research Institute, a program of Lawson. She is also Assistant Professor in the Department of Epidemiology & Biostatistics at the Schulich School of Medicine & Dentistry, Western University.
“I lead a research program in public mental health research, with a primary focus on young people experiencing a first onset of psychotic disorder. Together with my team, we are investigating the distribution and risk factors for psychotic disorders, prevention in early psychosis, and access to care and utilization of services in first-episode psychosis. My research program is centered around mentorship and training of students from all levels, and I work with trainees to foster high-level skills in the design and analysis of epidemiologic studies using large complex datasets. I am committed to fostering a culture of equity, diversity, and inclusion within my research team, and I advocate strongly for gender and early career representation for awards, scientific symposia, and other career opportunities. As a female scientist, I regularly mentor young women, both formally and informally, and due to the focus of my research, I also regularly work with trainees with lived experience of mental disorders. The diverse experiences and perspectives of these students both inspire and inform our work together.”
Dr. Michelle Barton-Forbes is an Associate Scientist at Lawson and a Physician at London Health Sciences Centre (LHSC) specializing in paediatric infectious diseases. She is also an Assistant Professor at the Schulich School of Medicine & Dentistry, Western University.
“My research program is focused on the clinical epidemiology of infectious diseases in children, particularly in vulnerable paediatric populations such as neonates and young infants. A secondary area of interest is in bacterial resistance and antimicrobial stewardship. Through engagement in multicentre research and contribution to national guideline development, I am able to make a difference in the management and prevention of common childhood infections nationally. The combination of intense passion for my subspecialty, inquisitive curiosity and a drive to better understand common childhood illnesses is infectious to my students. I motivate my students to excellence by inspiring them to believe in themselves and their ability to make a difference. My students are encouraged and challenged to find answers to unanswered questions and unexplained trends through research. As a proud Canadian and an immigrant from a nation that prides itself in its diversity, I believe that diversity is our strength. The Jamaican national motto “out of many one people” has framed my worldview and has influenced my practice.”
Dr. Eileen Crowley is a Scientist at Lawson and a Pediatric Gastroenterologist at LHSC. She is also an Assistant Professor at the Schulich School of Medicine & Dentistry, Western University.
“My research interests include pediatric inflammatory bowel disease (IBD), the genetics of IBD, big datasets, therapeutic drug monitoring clinical trial endpoints and precision medicine. My work has served to be better delineate the genetic phenotype of children with IBD as well as optimizing response to therapy in this age group. I engage students and motivate them to work with enthusiasm! My aim is to create learning opportunities that are active, collaborative and promote learning relationships. Once I have identified a student’s goal, it is easier to share and attain that goal. Within the research setting, I aim to maintain an environment where every student feels accepted, valued and safe. Sharing of ideas creates opportunities whilst also fostering a sense of personal belonging and achievement.”
To learn more about International Women’s Day, visit https://www.internationalwomensday.com/.