Fecal microbiota transplantation may enhance the effectiveness of immunotherapies by reducing gut dysbiosis, according to a presentation at the 2025 ASCO Annual Meeting, in Chicago. However, antibiotics should be used sparingly in people receiving immunotherapies, in short stints after an infection, as the overuse of antibiotics may increase dysbiosis and could potentially inhibit the effectiveness of FMT.

“Dysbiosis is a key biomarker of response and resistance to immunotherapy; the goal of FMT is to replace the diseased dysbiotic microbiome of a patient with that of a donor microbiome,” said ASCO speaker Arielle Elkrief, MD, FRCPC, the co-director of the CHUM Microbiome Centre, in Montreal. The FMT procedure does not generally require antibiotics, but short courses of antibiotics may be needed if FMT causes an infection.

“Fecal microbiota transplantation is safe and potentially increases immunotherapy activity across multiple histologies,” Dr. Elkrief said. Two phase 1 studies Dr. Elkrief cited tested whether an FMT donation from people who had benefited from immunotherapy helped melanoma patients who were refractory to immunotherapy. It did, with post-FMT objective response rates (ORRs) of 20% to 30% (Science 2021;371[6529]:595-602 and 602-609).

These results prompted the phase 2 FMT-LUMINate trial, for which Dr. Elkrief is an investigator. This effort showed ORRs for FMT of, respectively, 80% in people with non-small cell lung cancer and 75% in those with melanoma (Cancer Res 2024;84[7 suppl]:CT258).

Limited Availability of FMT, but Widespread Use of Antibiotics

FMT is not readily available, Dr. Elkrief noted, due to challenges with getting enough donors of fecal material. In her lab and others, researchers are developing live biotherapeutic products that mimic the action of FMT.

Dr. Elkrief noted there is no evidence that over-the-counter probiotics will improve gut dysbiosis in people with cancer. Indeed, one study she cited suggests that the gut microbiome takes longer to recover in people who receive probiotics rather than FMT (Cell 2018;174[6]:1406-1423.e16). Another study found an association with shorter progression-free survival (PFS) and taking probiotics in 128 people with melanoma (Science 2021;374[6575]:1632-1640).

Given FMT’s limited availability, some patients taking immunotherapies won’t be able to benefit from it. However, many people taking immunotherapies will have access to antibiotics, which can be vital after infections—but it’s important not to overuse antibiotics in this situation, Dr. Elkrief stressed.

“Antibiotic stewardship is key to decreasing antibiotic-related dysbiosis and improving outcomes to immunotherapy for patients with cancer,” Dr. Elkrief said.

A 2018 study cited by Dr. Elkrief, co-authored with CHUM colleague Bertrand Routy, MD, PhD, documented the potential risks of antibiotics for people with cancer. Patients who received immune checkpoint inhibitors for lung cancer plus antibiotics had shorter PFS (median, 1.9 vs. 7.4 months; hazard ratio [HR], 3.1; 95% CI, 1.4-6.9; P<0.01) and shorter overall survival (median, 17.3 vs. 30.6 months; HR, 3.5; 95% CI, 1.1-10.8; P=0.03) than those who only received immune checkpoint inhibitors (Ann Oncol 2018;29[6]:1437-1444). A 2024 study, with

Dr. Elkrief as first author, validated these findings in a larger cohort of people with lung cancer (NPJ Precis Oncol 2024;8[1]:143).

“We know that antibiotics can be lifesaving,” Dr. Elkrief said. “When infections happen, we recommend a short course, a narrow spectrum and to reassess the need for antibiotics constantly” in consultation with experts in infectious disease.

—Marcus A. Banks

Dr. Elkrief reported financial relationships with AstraZeneca, Bristol Myers Squibb and Merck.

Originally published by our sister publication Pharmacy Practice News