FMT helps half of patients with GI cancers overcome immunotherapy resistance (Jul 2024) Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor FMT

[Michael Harrop]

https://medicalxpress.com/news/2024-07-clinical-trial-fecal-transplant-patients.html
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00228-2

The trial included patients with metastatic solid-tumor cancers who were resistant to the anti-PD-1 drug nivolumab. Four had gastric cancer, five had esophageal cancer, and four had hepatocellular carcinoma.

The six FMT donors, who also had gastric cancer, esophageal cancer, or hepatocellular carcinoma, had had a complete or partial response for at least six months after treatment with nivolumab or pembrolizumab. The FMTs were given via colonoscopy after the recipients had received antibiotics to tamp down their own microbiotas.

One of the most surprising results was from a hepatocellular carcinoma patient who initially showed no response to the first FMT and continued to experience cancer progression. However, after switching the donor for the second FMT, the patient exhibited remarkable tumor shrinkage

they identified a novel bacterial strain that helped to improve FMT efficacy, Prevotella merdae Immunoactis

They also identified two strains that had a detrimental impact on FMT efficacy, Lactobacillus salivarius and Bacteroides plebeius

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Highlights​

• FMT with anti-PD-1 shows benefits in advanced solid cancers resistant to anti-PD-1
• FMT induced partial response to anti-PD-1 in R7 recipients with enhanced immunity
• Lactobacillus salivarius and Bacteroides plebeius may inhibit T cell activity
• Prevotella merdae Immunoactis boosts T cell activity and reduces tumor growth

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Summary​

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers.

FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity.

Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.

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Graphical abstract​

Adverse events:​

List on pg 25 https://www.cell.com/cms/10.1016/j.chom.2024.06.010/attachment/4aaf6335-9fb8-4380-8892-71871dd1fd25/mmc1

Skin rash
Skin pruritus
Hypothyroidism
Adrenal insufficiency
Myalgia
Fever
Gastritis

I'm not seeing how long they tracked adverse events for. IE: are patients developing new conditions months later? I only see this:

About 11 weeks after the second FMT, the patient experienced progressive epigastric pain and nausea, diagnosed as immune-related gastritis

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Regarding safety profiles, treatment-related adverse events (AEs) were minimal (Table S2). Out of the thirteen patients, seven patients (53.8%) experienced at least one treatment-related AE, all of which were either grade 1 or 2, except for one patient who experienced grade 3 immune-related gastritis. The most common treatment-related AEs were skin pruritus (n = 5, 38.5%), followed by skin rash (n = 2, 15.4%), and hypothyroidism (n = 2, 15.4%). Endocrine AEs were managed with hormone replacement therapy, and immune-related gastritis (CTCAE; Common Terminology Criteria for Adverse Events, grade 3) was managed with systemic corticosteroids.

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Half the patients experienced adverse events, which included gastritis and hypothyroidism, requiring hormone replacement therapy, and you call that "minimal"?? I guess it's "minimal" compared to dying of cancer, but I think this completely supports my position:

Another letter to the NIH (and FDA). Cancer patients as FMT donors. If you care about the future of FMT please consider also writing to them. (Mar 2019)