PT - JOURNAL ARTICLE AU - Robert I Haddad AU - Tanguy Y Seiwert AU - Laura Q M Chow AU - Shilpa Gupta AU - Jared Weiss AU - Iris Gluck AU - Joseph P Eder AU - Barbara Burtness AU - Makoto Tahara AU - Bhumsuk Keam AU - Hyunseok Kang AU - Kei Muro AU - Andrew Albright AU - Robin Mogg AU - Mark Ayers AU - Lingkang Huang AU - Jared Lunceford AU - Razvan Cristescu AU - Jonathan Cheng AU - Ranee Mehra TI - Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma AID - 10.1136/jitc-2021-003026 DP - 2022 Feb 01 TA - Journal for ImmunoTherapy of Cancer PG - e003026 VI - 10 IP - 2 4099 - http://jitc.bmj.com/content/10/2/e003026.short 4100 - http://jitc.bmj.com/content/10/2/e003026.full SO - J Immunother Cancer2022 Feb 01; 10 AB - Background To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study.Methods Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (TcellinfGEP), and PD-L1 combined positive score (CPS)) and clinical outcomes with pembrolizumab were assessed in patients with R/M HNSCC (n=192). Tumor human papillomavirus (HPV) status was also evaluated with the use of p16 immunohistochemistry and whole exome sequencing (WES; HPV+, mapping >20 HPV reads) in pretreatment tumor samples (n=106).Results TMB, clonality-weighted TMB, and TcellinfGEP were significantly associated with objective response (p=0.0276, p=0.0201, and p=0.006, respectively), and a positive trend was observed between NL and PD-L1 CPS and clinical response (p=0.0550 and p=0.0682, respectively). No correlation was observed between TMB and TcellinfGEP (Spearman ρ=–0.026) or TMB and PD-L1 (Spearman ρ=0.009); a correlation was observed between TcellinfGEP and PD-L1 (Spearman ρ=0.511). HPV status by WES and p16 immunohistochemistry showed concordance (84% ҡ=0.573) among patients whose HPV results were available using both methods.Conclusions TMB and inflammatory biomarkers (TcellinfGEP and PD-L1) may represent distinct and complementary biomarkers predicting response to anti-programmed death 1 therapies in HNSCC; further study of these relationships in randomized clinical trials is needed.Trial registration number NCT01848834.