In one of the first in-human studies to investigate whether modifying the gut microbiome by a fecal microbiota transplant could make cancer immunotherapy more effective, researchers analyzing this in ten cancer patients with refractory melanoma suggest the treatment can improve patient outcomes. Their results - which show a positive response in three out of the ten patients analyzed - are reported from a Phase 1 clinical trial. Though noting some limitations of their work, the authors say their findings support the concept of overcoming resistance to immunotherapy by modulating the gut microbiota. Many cancer patients who receive PD-1 blockade therapy do not respond to it, developing resistance. Among the most promising routes for overcoming resistance to anti-PD-1 therapy is altering the gut microbiome, which has been shown to influence the response of tumors to anti-PD-1 immunotherapy in pre-clinical mouse models and observational patient cohorts. While no specific bacterial taxa have been consistently associated with this response, fecal microbiota transplantation (FMT) - which transfers the entire gut microbiota from one host to another - has demonstrated promising results in pre-clinical models. Based on this data, Erez N. Baruch and colleagues designed a Phase 1 clinical test to evaluate how FMT, followed by re-initiation of anti-PD-1 immunotherapy, affected ten patients with metastatic melanoma who'd previously grown resistant to anti-PD-1 treatment. The transplant material was from one of two melanoma patients ("Donor 1" or "Donor 2"), both of whom had responded positively to anti-PD-1 therapy for at least one year. After receiving FMT from Donor 1 or Donor 2, three out of ten patients responded to subsequent anti-PD-1 treatment, as defined by regression of tumor size. All three had received their FMT from Donor 1, the authors note. The reason for the positive response as derived from Donor 1 alone is not clear, they say, as the study was statistically powered to assess safety and not to compare efficiency between donors. Even as the results offer no clear association between specific taxa and clinical response to FMT, however, they point to the combination of FMT and re-induction of anti-PD-1 therapy being "safe, feasible and potentially effective," say Baruch and colleagues.
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Journal
Science