36P - Exploring the role of soluble B7-H3 (sB7-H3) as a biomarker to predict the clinical benefit and/or the occurrence of immune related adverse events (irAEs) in advanced cancer patients treated with immune checkpoint inhibitors (ICIs)

Background

ICIs targeting programmed death cell 1 (PD-1) and its ligand 1 (PD-L1) revolutionized the management of many types of tumors. However, almost half of treated patients do not achieve any clinical benefit while another portion of patients (10-15%) develop severe irAEs. Consequently, biomarkers are needed to identify which patients have a higher likelihood of achieving a clinical benefit and/or developing severe irAEs.

Methods

We assessed the role of sB7-H3 as a biomarker for predicting the clinical benefit and the occurrence of irAEs in advanced cancer patients treated with ICIs. sB7-H3 levels were evaluated by ELISA assay before starting (T0) and after three months of anti PD-1/PD-L1 therapy (T1). Clinical-pathological characteristics and sB7-H3 levels were correlated with survival outcomes (PFS and OS) using log-rank test. Grade 1-2 and 3-4 irAE rates were correlated with the levels of sB7-H3 using one-way ANOVA.

Results

Sixty-four patients including non-small cell lung cancer (36), renal cell carcinoma (16), head and neck squamous cell carcinoma (6) and melanoma (6) were treated with anti-PD-1/PD-L1 therapy as second-line therapy. At a median follow-up of 25.37 months, median PFS and OS were 7.13 and 10.80 months, respectively. Grade 1-2 and grade 3-4 irAEs were reported in 52 (81.25%) and 10 (15.63%) of treated patients, respectively. The levels of sB7-H3 both at T0 and T1 were significantly correlated with PFS (p=0.048 and 0.05) and OS (p=0.018 and 0.042). Specifically, patients displaying lower levels of sB7-H3 have an increased PFS and OS as compared to those with higher levels. In addition, lower levels of sB7-H3 both at T0 and T1 were correlated with the occurrence of grade 3-4 irAEs (p= 0.005 and p=0.001). No further significant correlation between clinical-pathological characteristics and survival outcomes or sB7-H3 levels was found.

Conclusions

Our findings have clinical relevance since i) identify sB7-H3 as an efficient biomarker for predicting clinical benefit and occurrence of irAEs in advanced cancer patients treated with ICIs; and ii) propose B7-H3 as a mechanism of resistance to ICIs.

Legal entity responsible for the study

Prof Francesco Sabbatino.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.