Abstract 841P
Background
The combination of immune checkpoint inhibitors (ICIs) with molecular targeted drugs or chemotherapy has been explored to improve the clinical benefit of cancer therapy. However, the effect of combination therapy on the gut microbiota has not been characterized.
Methods
We retrospectively analyzed frozen fecal samples for gut microbiota genomic characterization. A total of 50 pantients’ samples of advanced melanoma who received ICI-based therapy from Sun Yat-sen University Cancer Center were included. Fecal samples were collected at various time points during the immunotherapy. Total DNA was extracted from the fecal samples and sequenced. The filtered gut microbiome DNA reads were mapped to the integrated gene catalogue.
Results
We examined the longitudinal changes in gut microbiota composition in patients that received ICI monotherapy (anti-PD-1 therapy; n=23), combined ICI with chemotherapy [nab-paclitaxel (PTX) or temozolomide (TMZ); n=13], or molecular targeting drugs [vemurafenib, or lenvatinib/anlotinib (TKI); n=14]. In 7 patients who received both ICI monotherapy and combination therapies, we found reduced gut bacterial richness and alpha diversity upon ICI combination therapies. ICI combination therapies also altered gut bacterial species abundances more intensively than ICI monotherapy. The abundance of the Bacteroides genus was increased while the abundance of the Eubacterium and Clostridium genus were decreased after combination therapies. Furthermore, bacterial species characteristics of specific combination regimens were identified. Akkermansia muciniphila was found to be more abundant in ICI plus TKI, and Clostridium disporicum was more abundant in ICI plus TMZ compared with ICI alone. ICI plus PTX displayed higher abundance of Parabacteroides genus than all other groups. Several bacterial species including Ruthenibacterium lactatiformans were found to be enriched in ICI plus vemurafenib. Interestingly, Ruthenibacterium lactatiformans was found to be highly enriched in non-responders of ICI alone.
Conclusions
Our study points to a possible effect of ICI based combination therapies on the gut microbiota and provides implications for the treatment of advanced melanoma patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
L. Xu.
Funding
National Natural Science Foundation of China (Grant number: 81802725).
Disclosure
All authors have declared no conflicts of interest.