From the Journals

Study links gut microbiome and mRCC treatment outcomes



New research, published in European Urology, has revealed an association between gut microbial diversity and treatment outcomes for patients with metastatic renal cell carcinoma receiving checkpoint inhibitor therapy.

The findings suggest that metastatic renal cell carcinoma (mRCC) patients with a greater abundance of certain bacterial species derive clinical benefit from checkpoint inhibitor (CPI) treatment.

“We conducted a prospective observational study to determine the association between baseline gut microbial diversity and clinical benefit in patients with mRCC receiving CPIs,” study author Nicholas J. Salgia, an MD/PhD student at the State University of New York at Buffalo, and colleagues wrote.

The researchers collected stool samples from 31 mRCC patients within 7 days of them starting nivolumab monotherapy (77%) or nivolumab plus ipilimumab (23%). The microbial composition of each sample was evaluated using whole-metagenome sequencing at baseline, 1 month, and 3 months following treatment initiation.

In all, 58% of patients experienced a clinical benefit of treatment, which was defined as achieving a response or having stable disease for more than 4 months. There were 11 patients (35%) who achieved a complete or partial response and 7 (23%) who had stable disease for more than 4 months.

“Greater microbial diversity was associated with clinical benefit from CPI therapy (P = .001), and multiple species were associated with clinical benefit or lack thereof,” the researchers wrote.

In fact, there were 13 bacterial species with a linear discriminant analysis score of 3 or greater that distinguished between patients who had a clinical benefit (9 species) and those who did not (4 species).

The bacterial species with the greatest significance among patients with a clinical benefit were Bifidobacterium adolescentis (P = .002), Barnesiella intestinihominis (P = .002), Odoribacter splanchnicus (P = .006), and Bacteroides eggerthii (P = .009).

“These results suggest that certain species (e.g., [Prevotella] copri) appear to expand in relative abundance in patients deriving clinical benefit,” the researchers wrote.

The team also found that Akkermansia muciniphila increased in relative abundance in many patients experiencing clinical benefit and decreased in several patients not deriving clinical benefit.

“The patients with the highest benefit from cancer treatment were those with more microbial diversity but also those with a higher abundance of a specific bacterium known as Akkermansia muciniphila,” study author Sarah K. Highlander, PhD, of Translational Genomics Research Institute in Phoenix, said in a statement.

“This organism has been associated with benefit in other immunotherapy studies,” she explained.

The researchers acknowledged that a key limitation of this study was the method of stool collection. Given the use of a small, non–vacuum-sealed container, proliferation of aerobic bacteria could have occurred.

Based on the findings of this study, researchers are conducting a randomized clinical trial to evaluate the role of gut microbial modulation in CPI response. In this phase 1 study, researchers are investigating the use of frontline nivolumab plus ipilimumab, with or without CBM-588, a strain of Clostridium butyricum with both anti-inflammatory and immunomodulatory properties in the intestinal epithelium.

The current study was supported, in part, by a grant from Bristol-Myers Squibb. Several authors disclosed financial affiliations with multiple pharmaceutical companies.

SOURCE: Salgia NJ et al. Eur Urol. 2020 Aug 2. doi: 10.1016/j.eururo.2020.07.011.

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