High Tumor Mutational Burden May Predict Improved Response to Immunotherapy in Head and Neck Cancer Patients

• Published in: International journal of radiation oncology, biology, physics Vol. 118; no. 5; p. e43
• Main Authors: Stewart, M., Reddy, C.A., Woody, N.M., Sussman, T., Yilmaz, E., Geiger, J.L.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2024
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2024.01.097

Tumor mutational burden (TMB) is an emerging biomarker utilized in some cancers as a predictive tool to determine benefit to immune checkpoint inhibitor therapy and high TMB alone is an indication for pembrolizumab monotherapy, tumor agnostic. For head and neck squamous cell carcinoma (HNSCC), there is limited data utilizing TMB as a biomarker to predict response to PD-L1 inhibitors. This study assesses TMB score and progression of disease in HNSCC patients treated with immunotherapy. From an IRB-approved database, we retrospectively analyzed 51 patients treated between 2016 and 2023 with HNSCC who had at least one dose of pembrolizumab and known next generation sequencing (NGS). Patients were stratified between high TMB (≥10 mutations/Mb) and low (<10 mutations/Mb). Of the 51 patients, 40 (78%) had progression of disease while on pembrolizumab. The median TMB of those who progressed was 6.9 mutations/Mb. The median time to disease progression was 5.8 months. There were 37 patients who were classified as low TMB with a median 5.0 mutations/Mb. Of these 37, 29 (78%) had progression while on pembrolizumab with a median time to progression of 3.5 months. For the 14 patients with high TMB scores, the median was 12.0 mutations/Mb. Of these 14, 11 (79%) had progression while on pembrolizumab with a median time to progression of 5.8 months. There was no statistical difference in time to progression between high and low TMB cohorts (p=0.3483). Of the 11 (22%) without progression, all patients started pembrolizumab in the setting of recurrent HNSCC (7 metastatic, 4 locoregionally recurrent). The majority in this cohort are classified as having low TMB (n=8/11) with a median TMB of 5.0 mutations/Mb. Of the 10 patients who actively remain on pembrolizumab, they have been on pembrolizumab for a median of 14.7 months. A multivariable analysis revealed that TMB as a continuous variable (i.e., increase in TMB mutations), the risk of progression decreased (p=0.0238, HR 0.940). Although there was no statistical difference in time to progression between our high TMB and low TMB cohorts, a higher TMB score correlated with decreased risk of progression in our cohort of HNSCC patients. Further research is needed to better understand the utility of TMB as a biomarker in HNSCC.