37P - Lymphocyte Subpopulation Balances as a Blood Biomarker for Immune-Related Adverse Events in Patients Receiving Immune Checkpoint Inhibitors

Background

Immune-related adverse events (irAEs) are a major concern for cancer patients treated with immune checkpoint inhibitors (ICIs) largely due to the absence of reliable predictive biomarkers. While irAEs can often be managed with immunosuppressive drugs, this comes at the cost of decreasing ICI-induced anti-tumor immunity. Tertiary lymphoid structures (TLS) and T follicular helper cells (Tfh), have been shown to play an important role in tumor control and ICI responsiveness, and might also play a role in irAEs pathogenesis due to their involvement in autoimmunity, B cell activation, Th1-skewed CD4+ and CD8+ T cell activation.

Methods

We analyzed blood from ICI-treated patients with solid tumors (n=35) from our ongoing prospective clinical trial (NCT05429866). Samples were collected at baseline (pre-ICI), periodically during treatment, and at the onset of any irAE (grades 1-4) before intervention. Fresh blood was immunophenotyped by flow cytometry.

Results

The patients included: melanoma (n=14), NSCLC (n=10), endometrial cancer (n=4), breast cancer (n=3), GI cancer (n= 1), head/neck cancer (n=1), RCC (n=1) and urothelial cancer (n=1), treated with ICI alone (n=21) or with chemotherapy (n=14). At 12 months of follow-up, 47.1% had experienced an irAE with 80.8% grade 1-2 and 19.2% grade 3-4. Neutrophil counts (P=0.02) and the neutrophil/lymphocyte ratio (P=0.05) were higher at baseline in patients experiencing an irAE. Furthermore increases in the percent of total CD4+ (P=0.03), Th1 (P=0.04), and Tfh1 (P=0.01) cells, coupled with decreases in Th17 (P=0.003) and Tfh17 (P=0.03) cells in the blood at 8-11 weeks on treatment were significantly associated with an irAE.

Conclusions

These results suggest that changes in the relative balance of neutrophils and specific CD4+ T cell subpopulations were linked with an irAE. Our ongoing studies will further investigate changes in cytokine and gene expression profiles to deepen our understanding of these associations. This study marks a first step toward identifying biomarkers that anticipate the onset of an irAE and consequently reduce the need for immunosuppressive treatment that could compromise the efficacy of ICIs.

Clinical trial identification

NCT05429866.

Legal entity responsible for the study

The authors.

Funding

Association Jules Bordet.

Disclosure

All authors have declared no conflicts of interest.