Gut microbiome linked to RCC immunotherapy efficacy
medwireNews: Research has demonstrated an association between the gut microbiome composition and response to treatment with immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (RCC).
“This study substantiates results from previous [ICI]-related microbiome profiling studies” in this patient population, and extends the findings by providing a sequential analysis of the microbiome, say Sumanta Pal (City of Hope Comprehensive Cancer Center, Duarte, California, USA) and collaborators in European Urology.
All 31 of the study participants provided a baseline stool sample in the week prior to initiating treatment with nivolumab alone (77%) or alongside ipilimumab (23%), with 84% and 39% also providing a sample at a median of 28 and 79 days after starting treatment, respectively.
Whole-metagenome analysis of the samples collected across the timepoints showed that the 58% of patients experiencing a clinical benefit from ICI therapy, defined as a complete or partial response or stable disease for at least 4 months, had significantly greater diversity of bacterial species according to the Shannon index than the 42% who had progressive disease.
The researchers also identified bacterial species that were significantly enriched in the microbiomes of patients deriving clinical benefit, these included Bifidobacterium adolescentis, Barnesiella intestinihominis, Odoribacter splanchnicus, and Bacteroides eggerthii.
By contrast, Bacteroides ovatus, Eggerthella lenta, and Fusicatenibacter saccharivorans were more common in the microbiomes of nonresponders.
Moreover, the relative abundance of Akkermansia spp. and Prevotella copri increased across the timepoints among participants deriving clinical benefit, while the abundance of Akkermansia muciniphila “decreased in many patients not deriving clinical benefit,” say Pal and colleagues.
“Although we did not find an association between baseline A. muciniphila and clinical benefit, this has been implicated in a previous study,” they continue.
The authors highlight the limitations of the study, including the method of stool collection, which could allow for propagation of aerobic bacteria, and the “approach of combining specimens across time points.”
Nevertheless, these findings “have led to the development of a phase 1 randomized clinical trial at our institution investigating the role of gut microbial modulation in [ICI] response,” using CMB-588, “a strain of Clostridium butyricum with immunomodulatory and anti-inflammatory effects in the intestinal epithelium,” alongside the standard front-line regimen of nivolumab plus ipilimumab, say Pal et al.
They hypothesize that “the agent may foster the development of a more favorable microbiome, including species cited herein that are associated with [ICI] response.”
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