Abstract 771P
Background
Immune checkpoint inhibition (ICI) has proven to be a major breakthrough in cancer treatment but often causes severe immune-related adverse events (irAEs). While gut microbiome composition has been associated with ICI efficacy, its role in irAE development is uncertain. This study aims to investigate the role of gut microbiome composition during ICI in severe irAE occurrence.
Methods
This prospective cohort study included cancer patients being treated with either combined CTLA-4 plus PD-1 blockade (cICI) or anti-PD-(L)1 monotherapy. Stool samples were collected before treatment initiation, early on-treatment and at onset of severe (i.e. ≥grade 3) irAEs. Using 16S rRNA gene sequencing (V3-V4 region), differences in gut microbiome composition (alpha diversity, beta diversity and differential relative abundances) were assessed between patients with and without severe irAEs, stratified by treatment regimen and sampling time point.
Results
Among 110 patients with valid baseline samples, 16 out of the 32 patients receiving cICI developed severe irAEs compared to 9 out of the 68 patients receiving anti-PD-(L)1. Before treatment, no differences in gut microbiome composition were observed between the two treatment groups. In 6/16 cICI treated patients with severe irAEs (38%), compared to 0/16 patients without severe irAEs (0%), we found a high relative abundance (>5%) of genus Escherichia-Shigella before treatment. In stool samples collected at severe irAE onset, high relative abundances (>10%) of either Escherichia-Shigella, Streptococcus or both were seen in 4/7 patients (57%), while no cICI treated patient without severe irAEs had such high relative abundances at any time point. No relevant differences in gut microbiome composition were observed among anti-PD-(L)1 treated patients with or without severe irAEs at any time point.
Conclusions
High relative abundances of the pro-inflammatory genera Escherichia-Shigella or Streptococcus before and during ICI treatment may be associated with severe irAE onset in cICI patients but not in anti-PD-(L)1 patients. Further studies are needed to elucidate the role of the gut microbiome in irAE pathogenesis, which can contribute to evidence-based irAE prevention and management.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UMC Utrecht.
Funding
KF Hein fund.
Disclosure
A.M. May: Non-Financial Interests, Institutional, Advisory Role: Compass. K.P.M. Suijkerbuijk: Non-Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb, Merck Sharp and Dome, AbbVie, Pierre Fabre, Novartis; Financial Interests, Institutional, Research Grant: TigaTx, Bristol Myers Squibb, Philips. All other authors have declared no conflicts of interest.