A phase 1 clinical trial exploring the use of fecal transplants to supplement immunotherapy treatment for melanoma has found it to be safe and has the potential to improve patients’ response to treatment.
More and more research has highlighted the importance of the gut microbiome to overall health and the development of diseases such as obesity, type 2 diabetes, intestinal bowel diseases and several cancers. Fecal transplants, the transfer of fecal bacteria and other microbes from a healthy individual into another, have emerged as a way of improving microbiome health and, thereby, combatting disease.
Melanoma is a type of skin cancer. In patients with advanced (Stage 4) melanoma – where it has spread from where it started to another part of the body – the go-to treatment is checkpoint inhibitor immunotherapy, which blocks the proteins that stop the immune system from attacking cancer cells. Unfortunately, nearly half of patients who receive a single checkpoint inhibitor develop resistance to the treatment.
A phase 1 clinical trial involving a trio of Canadian facilities – Lawson Health Research Institute, the Centre hospitalier de l’Université de Montréal and the Jewish General Hospital – tested whether supplementing immunotherapy with fecal transplantation was safe and how it affected the response of patients with advanced melanoma to immunotherapy treatment.
“In this study, we aimed to improve melanoma patients’ response to immunotherapy by improving the health of their microbiome through fecal transplants,” said John Lenehan, one of the study’s co-authors.
Phase 1 trials are the first step in testing new treatments in humans. They are essentially about ensuring patient safety and testing for side effects. Here, the researchers recruited 20 melanoma patients and gave them about 40 fecal transplant capsules orally in one session one week before they started immunotherapy treatment with a checkpoint inhibitor. Nineteen (95%) participants had Stage 4 melanoma, including three with brain metastases.
Regarding safety, the trial’s primary concern, eight patients (40%) experienced low-grade adverse effects from the FMT, such as diarrhea, flatulence and abdominal discomfort, but all patients completed FMT treatment. Five (25%) patients experienced adverse events due to the immunotherapy, leading to discontinuation of the treatment. The researchers concluded that the combination therapy was safe.
The second aim of the trial was to assess the clinical efficacy of combining FMT and immunotherapy. In this regard, the researchers found that 65% of patients had an "objective response", as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, including 4 patients who achieved a complete response (disappearance of all target lesions), and 9 patients who achieved a partial response (at least a 30% decrease in diameter of target lesions). Of those patients, 20% achieved a complete response (disappearance of all target lesions), and 45% achieved a partial response (at least a 30% decrease in diameter of target lesions).
“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,” said Wilson Miller, one of the study’s co-authors.
The researchers also found that patients’ microbiomes increased in diversity which was maintained over time regardless of how they responded clinically to immunotherapy treatment. They say their study’s findings can potentially change how we think about treating cancer.
“We have reached a plateau in treating melanoma with immunotherapy, but the microbiome has the potential to be a paradigm shift,” said Bertrand Routy, lead author of the study.
The study was published in the journal Nature Medicine.
Source: Lawson Health Research Institute
