Hassane M. Zarour and colleagues in their phase 1 clinical trial in 2020, investigated if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti-programmed death 1 immunotherapy.

Although the response of tumors to anti–PD-1 immunotherapy has been demonstrated in mice, FMT still demands evaluation in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. 

They enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs. 7 patients with advanced melanoma who responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months were the donors.

Donor-derived FMT was given to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. 6 out of 15 recipients responded to treatment, with a reduction in tumor or long-term disease stabilization along with an increased abundance of taxa that were earlier linked with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

Similar results were obtained from an Israeli study where the FMT protocol included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The FMT donors were previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. 1 of the 10 FMT recipients showed a complete response and 2 demonstrated a partial response.

Source: Brunk D. Fecal microbiota transplants may improve resistance to melanoma immunotherapy, Dermatology News, October 2021.