Article Text

Download PDFPDF

19 Peripheral lymphocytes and lactate dehydrogenase correlate with improved response and survival in head and neck cancer treated with immune checkpoint inhibitors
  1. Cassie Pan1,
  2. Qian ‘Vicky’ Wu2,
  3. Jenna Voutsinas2,
  4. Jeffrey Houlton1,
  5. Brittany Barber1,
  6. Zain Rizvi1,
  7. Emily Marchiano1,
  8. Neal Futran1,
  9. George Laramore1,
  10. Jay Liao1,
  11. Upendra Parvathaneni1,
  12. Renato Martins3,
  13. Jonathan Fromm1 and
  14. Cristina Rodriguez1
  1. 1University of Washington, Seattle, WA, USA
  2. 2Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  3. 3Virginia Commonwealth University, Richmond, VA, USA


Background Little is known regarding peripheral blood biomarkers (PBBMs) for oncologic outcomes in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). We explored associations of PBBMs with outcomes and toxicities in R/M HNSCC treated with ICIs.

Methods In this single-institution retrospective cohort study, records of 186 adult patients with R/M HNSCC treated with ICIs between 08/2012–03/2021 were reviewed. Pretreatment PBBMs investigated included lactate dehydrogenase (LDH), platelets, neutrophils, lymphocytes, monocytes, eosinophils, neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI). Percent (%) and absolute (abs) values for each cell type were examined. Cox regression was performed to explore associations with time-to-event outcomes, including overall survival (OS) and progression-free survival (PFS). Logistic regression was performed for binary outcomes, including objective response (ORR) by RECIST 1.1 and grade ≥3 toxicities (G≥3AE) by CTCAEv5 within 100 days of treatment initiation. Multivariable models for each outcome were created using elastic net variable selection method.

Results Median age was 64 (range 24–90), 145 (78%) were male, 149 (82%) had ECOG ≤1, 81 (44%) were never-smokers, and 60 (33%) had p16-positive tumors. Single-agent pembrolizumab or nivolumab was used in 140 (75%) patients. Combined positive score (CPS) was available in 33 patients, with median CPS 31 (range 0–100). Univariate analyses adjusted for ECOG, p16, and smoking revealed that baseline higher LDH (p=0.025), neutrophils (%: p=0.002, abs: p=0.001), monocytes (abs: p=0.043), and NLR (p<0.001), and lower lymphocytes (%: p<0.001, abs: p=0.005), eosinophils (%: p=0.046), and PNI (p=0.005) correlated with worse OS. Elevated platelets (p=0.010), neutrophils (%: p=0.010, abs: p<0.001), and NLR (p<0.001), and decreased lymphocytes (%: p<0.001) and PNI (p=0.007) correlated with worse PFS. No peripheral blood parameter reached significance for G≥3AEs or ORR, although% lymphocytes, absolute neutrophils, and LDH were borderline significant for ORR (p=0.066, p=0.055, p=0.069, respectively). Refitted multivariable models adjusted for ECOG, p16, and smoking confirmed that lower% lymphocytes and higher LDH and absolute neutrophils correlated with worse OS and PFS. Lower% lymphocytes and higher LDH also correlated with worse ORR.

Conclusions In the largest cohort to date of R/M HNSCCs treated with ICIs, our variable selection method showed that baseline lower% lymphocytes and higher LDH and absolute neutrophils correlated with worse OS and PFS, and lower% lymphocytes and higher LDH correlated with worse ORR. PBBMs are promising prognostic tools for immunotherapy in HNSCC and warrant further investigation in a large, prospective study along with validation with CPS biomarker.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.