Neutrophil to lymphocyte ratio and peripheral blood biomarkers correlate with outcomes among patients with recurrent metastatic head and neck squamous cell carcinoma and salivary gland cancer treated on a phase II trial of pembrolizumab and vorinostat

Presentation: AHNS05
Topic: Immunotherapy / Systemic Therapy
Type: Oral
Date: Wednesday, April 27, 2022
Session: 11:15 AM – 12:00 PM Cancer Biology
Authors: Cassie Pan1; Qian (Vicky) Wu2; Jenna Voutsinas2; Jeffrey J Houlton1; Brittany Barber1; Neal Futran1; Renato G Martins3; Jonathan R Fromm4; Cristina P Rodriguez3
Institution(s): 1Department of Otolaryngology, University of Washington, Seattle, WA; 2Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 3Division of Oncology, Department of Medicine, University of Washington, Seattle, WA; 4Department of Laboratory Medicine, University of Washington, Seattle, WA


Peripheral blood markers predictive of outcomes and toxicity to immune checkpoint inhibitors are unexplored in head and neck malignancies. Our group has published a phase II clinical trial (Clin Cancer Res 2019, NCT02538510) of pembrolizumab and vorinostat (P+V) among recurrent/metastatic head and neck squamous cell carcinoma (HN) and salivary gland cancer (SGC) and obtained peripheral blood correlatives. We sought to explore associations between peripheral blood biomarkers and oncologic outcomes as well as toxicity.

Methods: Patients with progressing incurable HN and SGC were enrolled and received P 200 mg intravenous every 21 days and V 400 mg orally 5 days on/2 days off during each 21-day cycle. Correlative blood samples were collected at baseline and after three cycles of P+V when possible. LSRII flow cytometry (BD Biosciences) was performed on these samples using Woodlist 3.1 software to characterize baseline and on-treatment peripheral T cell phenotypes, including CD3+/CD4+ (helper) and CD3+/CD8+ (cytotoxic) T cells, as well as PD1 and PDL1 expression on CD4+ and CD8+ T cells. Additionally, baseline and on-treatment neutrophils, lymphocytes, platelets and neutrophil-to-lymphocyte ratio (NLR) were obtained. Combined positive score (CPS) was not routinely obtained during this time period. Univariable Cox regression was performed to explore associations between a covariate of interest (e.g., T cell phenotypes) and time-to-event outcomes, such as overall survival (OS) and progression free survival (PFS). Logistic regression was performed with binary outcomes, such as objective response (ORR) based on RECIST 1.1 criteria and grade ≥3 toxicities (G≥3AE) based on CTCAEv5.

Results: This trial enrolled 25 HN and 25 SGCs between 11/2015 and 8/2017. Outcome results were previously published. Baseline peripheral blood was available in 21 HN and 20 SGCs. Lower baseline NLR correlated with improved OS (HR 1.12, [95% CI 1.04-1.20], p=0.001), PFS (HR 1.11, [1.04-1.19], p=0.001), and lower rates of G≥3AE (OR 1.09, [1.00-1.19], p=0.04). Additionally, superior OS and PFS were associated with lower baseline absolute neutrophils (OS: HR 1.43, [1.17-1.75], p=0.0005) (PFS: HR 1.28, [1.09-1.51], p=0.003) and relative neutrophils (OS: HR 1.08, [1.02-1.13], p=0.004) (PFS: HR 1.07, [1.02-1.12], p=0.005), higher baseline relative lymphocytes (OS: HR 0.93, [0.88-0.99], p=0.021) (PFS: HR 0.93, [0.87-0.98], p=0.007), and higher baseline T helper cells (OS: HR 0.84, [0.75-0.95], p=0.005) (PFS: HR 0.84, [0.75-0.94], p=0.002). No relationship between ORR and any peripheral biomarker was observed.

Conclusions: In a small prospectively evaluated cohort of HN and SGCs treated with a combination of pembrolizumab and vorinostat, lower pretreatment NLR and neutrophils as well as higher pretreatment lymphocytes and T helper cells were associated with improved OS and PFS. Lower baseline NLR was further predictive of lower rates of serious adverse events. These peripheral blood biomarkers merit validation in a larger study and correlation with the validated CPS biomarker, as well as with more standard pembrolizumab monotherapy.