Abstract 1256: B-cell infiltration is associated with survival outcomes in nivolumab-treated head and neck squamous cell carcinoma (HNSCC): NCT 03652142
Authors: Gavrielatou Niki , Fortis Ekaterina , Spathis Aris , Anastasiou Maria , Economopoulou Panagiota , Gkotzamanidou Maria , Rusakiewics Sylvie , Vathiotis Ioannis , Aung Thazin Nwe , Kotsantis Ioannis , Vagia Elena Mihal , Panayiotides Ioannis , Rimm David , Coukos George , Foukas Periklis , Psyrri Amanda 
Published: June 2022

Background: Efficacy of Programmed Death1 inhibitor pembrolizumab in HNSCC demonstrates a positive correlation with PD-L1 expression, and PD-L1 positivity (CPS ≥1) is the only clinically approved biomarker for patient (pt) selection to this day. The primary objective of the current study is to prospectively explore candidate biomarkers from the tumor and tumor microenvironment for associations with clinical response to nivolumab in patients with recurrent/metastatic HNSCC treated with nivolumab.

Methods: Longitudinal tissue biopsies were collected from recurrent and/or metastatic HNSCC patients treated with nivolumab. Biopsies were taken at baseline, 24-72 hours after the second cycle of nivolumab and at progression. Biomarker analysis employing IHC/IF and flow cytometry was conducted. PD-L1 CPS was assessed for 47 cases. Utilizing IF staining, immune cell populations (CD3+/CD8+/CD20+/FOXP3+), were quantified in stromal and tumor segments of 44 evaluable baseline, 29 post-treatment and 9 PD biopsies. Flow cytometry for immune sub-phenotypes was also performed on 57, 29 and 13 samples at the same timepoints, respectively. Results were correlated with response by RECIST 1.1 and survival outcomes.

Results: High baseline CD20+ B cell density in stroma was associated with prolonged progression-free survival (PFS) (p=0.011) and the same trend was observed for overall survival (OS) (p=0.072). Intra-tumoral CD20+ did not demonstrate the same effect. None of the other immune-cell subtypes, in neither tissue compartment, were correlated with outcome. Increase in the post-treatment unswitched memory IgD/IgM+ B cell population in peripheral blood was also linked to improved OS (p=0.017). PD-L1 CPS ≥1 in baseline biopsies was associated with longer OS (p=0.001) but not PFS (p=0.12) and CD20+ B cell density was independent of PD-L1 positivity (p=0.121). When cases were stratified into 3 groups based on PD-L1 positivity and CD20+ B cell density, the “PD-L1/CD20+ double +/high” subgroup was associated with both improved PFS (p=0.013) and OS (p=0.028) in contrast with the “PD-L1/CD20+ single +/high” and “PD-L1/CD20+ double -/low” subgroups.

Conclusions: Overall, our findings uncover the implication of infiltrating CD20+ B cells in HNSCC nivolumab outcomes and underscore their ability to enhance the predictive value of PD-L1 CPS and thus further refine patient selection.

Citation Format: Niki Gavrielatou, Ekaterina Fortis, Aris Spathis, Maria Anastasiou, Panagiota Economopoulou, Maria Gkotzamanidou, Sylvie Rusakiewics, Ioannis Vathiotis, Thazin Nwe Aung, Ioannis Kotsantis, Elena Mihal Vagia, Ioannis Panayiotides, David Rimm, George Coukos, Periklis Foukas, Amanda Psyrri. B-cell infiltration is associated with survival outcomes in nivolumab-treated head and neck squamous cell carcinoma (HNSCC): NCT 03652142 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1256.