Dr Dizman on the Impact of CBM588 on the Gut Microbiome in ICI-Treated Patients With RCC

Nazli Dizman, MD, hematology/oncology fellow, The University of Texas MD Anderson Cancer Center, discusses results from a pooled analysis evaluating the impact of CBM588 on gut microbiome composition in patients with renal cell carcinoma (RCC) who received immune checkpoint inhibitors in the first line.

CBM588 is a nonpathogenic strain of Clostridium butyricumextensively utilized in Japan for various gastrointestinal cancers. Data from 2 randomized phase 1 clinical trials (NCT03829111; NCT05122546) investigating the efficacy of CBM588 revealed improvements in clinical outcomes. This prompted further investigation into the agent's impact on gut microbiome composition in patients with RCC through a pooled analysis of the studies.

The pooled analysis focused on microbiome diversity, a common metric in microbiome research, Dizman begins. Higher microbiome diversity has been linked to better outcomes with immune checkpoint inhibitors in prior studies, she states. However, findings presented at the 2024 Kidney Cancer Research Summit showed that the addition of CBM588 to checkpoint inhibitors did not result in an increase in diversity or improvement in the richness of the gut microbiome, Dizman reports. Despite the lack of increased diversity, CBM588 showed notable effects on specific bacterial species associated with positive outcomes in patients receiving immune checkpoint blockade therapies, Dizman continues. For instance, Eubacterium cerium, which typically declines in the standard of care arm, maintained stable abundance in the CBM588 arm. This suggests that CBM588 supplementation may help preserve beneficial bacterial species that are otherwise reduced during standard treatments, she explains.

Moreover, one of the most significant findings was CBM588’s ability to correct gut dysbiosis, Dizman emphasizes. Dysbiosis, an imbalance in the gut microbiome, is often characterized by a reduced ratio of beneficial bacteria. CBM588 increased the abundance of Bacteroidetes and simultaneously decreased the abundance of Firmicutes, she details. The resulting increase in the Bacteroidetes to Firmicutes ratio indicates a shift towards a more eubiotic, or balanced, gut microbiome, Dizman says. This shift suggests that CBM588 supplementation helps the microbiome evolve in a manner that supports overall health, potentially enhancing the efficacy of immune checkpoint inhibitors, she concludes.

These findings indicate that CBM588 could play a vital role in modulating the gut microbiome to improve clinical outcomes in cancer patients.