- In 2 of 3 patients with metastatic melanoma who had failed anti-programmed cell death protein 1 (PD-1) treatment, fecal microbiota transplant (FMT) resulted in clinical and radiological improvements with anti-PD-1 retreatment.
Why this matters
- Most patients with metastatic melanoma treated with PD-1 blockade do not achieve durable responses.
- Gut microbiota effects host immunity, and in murine models, FMT has enhanced anti-PD-1 effectiveness.
- Study subjects were 3 patients with metastatic melanoma who had failed at least 1 anti-PD-1 line of treatment. Each received FMT from 1 of 2 stool donors.
- Donors were 2 patients with metastatic melanoma who achieved a durable complete response to anti-PD-1 treatment.
- Recipients received FMT by both colonoscopy and oral ingestion of stool capsules followed by cycles of anti-PD-1 retreatment and maintenance FMT.
- Outcomes were measured by pre- and posttreatment stool sampling, tissue biopsy (gut and tumor), and total body imaging.
- Funding: None disclosed.
- Post-FMT stool 16S rDNA gene sequence analysis demonstrated compositional dissimilarity between the 2 recipient-donor groups, suggesting proper engraftment.
- Biopsies with immunohistochemical staining demonstrated increased post-FMT CD68+ cell infiltration in gut and tumor, and increased intrahumoral CD8+ T-cell infiltration.
- 2 of 3 patients who reached the 4-month follow-up point demonstrated durable clinical and radiological benefit from treatment.
- Small sample size with multiple interventions and no control arm.
- "This is a very difficult patient population," said Dr. Jennifer Wargo, a physician-scientist specializing in metastatic melanoma and microbiome research at MD Anderson Cancer Center in Houston, TX. It is remarkable that investigators found not only donor microbiome engraftment in study patients, but also changes in the immune microenvironment of the tumors themselves, she said. Although the sample size is very small, the results are encouraging, she said: "any response in these patients is a huge signal."