915P - Longer OS and RFS for CD3high/PD-L1+ head and neck squamous cell carcinoma (HNSCC) patients

Background

T cell infiltrates are associated with longer survival in HNSCC. For PD-L1 expression, aside of treatment targeting the PD1/PD-L1 axis, published data are equivocal. In this analysis, we combined CD3 density and PD-L1 expression in a cohort of HNSCC patients treated with surgery and risk-adapted adjuvant therapy.

Methods

IHC for CD3 and PD-L1 (E1L3N) was performed in a TMA with 457 HNSCC (triplicates). Digital image analysis (QuPath) was performed to measure CD3 densities (cells/mm²). PD-L1 expression was assessed in tumor and immune cells analogue to CPS. Overall survival (OS) and recurrence-free survival (RFS) in months were calculated using the Kaplan-Meier method and were compared by log-rank tests. A multivariable cox regression analysis was performed for T-, N-, HPV-status and CD3/PD-L1 (hot vs. cold).

Results

CD3 densities compared by primary tumor site were significantly different, whereas PD-L1 CPS were not. Median CD3 density of the respective primary site was used for binarization (CD3^high/low). 343 patients (pt) were evaluable for OS and 324 for RFS. CD3^high pt had longer median OS (p<0.001; not reached vs. 52.0 Mo) and RFS (p<0.001; 111,3 vs. 43.3 Mo) compared to CD3^low. Pt with PD-L1 expression CPS=1-19 and CPS20 had longer OS (p=0.009) and longer RFS (p=0.019) than pt with CPS<1 (CPS=1-19 vs CPS20 = ns). Binarization by CPS1 resulted in longer median OS (p=0,002; 111,3 vs. 49,3 Mo) and RFS (p=0.006; 98.3 vs. 41.0 Mo) compared to CPS<1. OS and PFS were significantly longer for CD3^high/CPS1 compared to all other combinations (p<0.001). CD3^low/CPS<1, CD3^low/CPS and CD3^high/CPS<1 did not differ significantly for OS or RFS. CD3^high/CPS1 (hot) was grouped against CD3^low/CPS<1, CD3^low/CPS and CD3^high/CPS<1 combined (cold). In a multivariable cox regression for OS, N-status (hazard ratio (HR) = 1.95), HPV-status (HR = 0.422) and “hot” (HR = 0.403) were independent prognostic markers. For RFS only “hot” was an independent prognostic marker (HR = 0.526).

Conclusions

The combination of CD3-density and PD-L1 expression performed superiorly in comparison to CD3 or PD-L1 alone. This may explain the equivocal impact of PD-L1 on OS and RFS. CD3-density combined with PD-L1 expression may identify patients who could benefit most from immunotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Laban: Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi Genzyme; Financial Interests, Institutional, Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Other, patent for an oropharyngeal cancer multi-peptide vaccine (pending): filed patent (patent pending); Non-Financial Interests, Principal Investigator: Immutep, Merck Sharp & Dohme, Bristol Myers Squibb, ISA-Pharmaceuticals. R. Remark: Financial Interests, Personal, Other, Employee: Innate Pharma. All other authors have declared no conflicts of interest.