FMT helps patients with advanced melanoma respond to MSD and BMS’ immunotherapies

Pharma News: For patients with cancers that do not respond to immunotherapy drugs, adjusting the gut microbiome may help some of these individuals respond to the immunotherapy drugs, a new study suggests.

In the trial conducted in collaboration with MSD, some patients with advanced melanoma who initially did not respond to treatment with an immune checkpoint inhibitor, did respond to the drug after receiving a transplant of faecal microbiota from a patient who had responded to the drug.

The results suggest that introducing certain faecal microorganisms into a patient’s colon may help the patient respond to drugs that enhance the immune system’s ability to recognise and kill tumour cells. The findings appeared in Science on February 4, 2021.

“In recent years, immunotherapy drugs called PD-1 and PD-L1 inhibitors have benefited many patients with certain types of cancer, but we need new strategies to help patients whose cancers do not respond,” said study co-leader Giorgio Trinchieri, M.D., chief of the Laboratory of Integrative Cancer Immunology in NCI’s Centre for Cancer Research. “Our study is one of the first to demonstrate in patients that altering the composition of the gut microbiome can improve the response to immunotherapy. The data provide proof of concept that the gut microbiome can be a therapeutic target in cancer.”

Changing the gut microbiome may “reprogram” the microenvironments of tumors that resist immunotherapy drugs, making them more favourable to treatment with these medicines, noted Dr. Trinchieri.

To test whether faecal microbiota transplants (FMT) are safe and may help patients with cancer better respond to immunotherapy, Dr. Trinchieri and his colleagues developed a single-arm clinical trial for patients with advanced melanoma. The patients’ tumours had not responded to one or more rounds of treatment with the immune checkpoint inhibitors pembrolizumab (Keytruda) or nivolumab (Opdivo), which were administered alone or in combination with other drugs.

In the study, the faecal transplants, which were obtained from patients with advanced melanoma who had responded to MSD’s Keytruda, were analysed to ensure that no infectious agents would be transmitted. After treatment with saline and other solutions, the faecal transplants were delivered to the colons of patients through colonoscopies, and each patient also received pembrolizumab.

After these treatments, 6 out of 15 patients who had not originally responded to MSD’s Keytruda or Bristol Myers Squibb’s Opdivo responded with either tumour reduction or long-term disease stabilisation. One of these patients has exhibited an ongoing partial response after more than two years and is still being followed by researchers, while four other patients are still receiving treatment and have shown no disease progression for over a year.

Based on the study findings, the researchers suggest that larger clinical trials should be conducted to confirm the results and identify biological markers that could eventually be used to select patients who are most likely to benefit from treatments that alter the gut microbiome.

“We expect that future studies will identify which groups of bacteria in the gut are capable of converting patients who do not respond to immunotherapy drugs into patients who do respond,” said Amiran Dzutsev, M.D., Ph.D., of NCI’s Centre for Cancer Research, co-first author of the study. “These could come from patients who have responded or from healthy donors. If researchers can identify which microorganisms are critical for the response to immunotherapy, then it may be possible to deliver these organisms directly to patients who need them, without requiring a faecal transplant,” he added.