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Clinical-genomic determinants of immune checkpoint blockade response in head and neck squamous cell carcinoma

Authors :
Cristina Valero
Mahdi Golkaram
Joris L. Vos
Bin Xu
Conall Fitzgerald
Mark Lee
Shannon Kaplan
Catherine Y. Han
Xin Pei
Reith Sarkar
Lillian A. Boe
Abhinav Pandey
Elizabeth S. Koh
Charlotte L. Zuur
David B. Solit
Traci Pawlowski
Li Liu
Alan L. Ho
Diego Chowell
Nadeem Riaz
Timothy A. Chan
Luc G.T. Morris
Source :
The Journal of Clinical Investigation, Vol 133, Iss 19 (2023)
Publication Year :
2023
Publisher :
American Society for Clinical Investigation, 2023.

Abstract

BACKGROUND Recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is generally an incurable disease, with patients experiencing median survival of under 10 months and significant morbidity. While immune checkpoint blockade (ICB) drugs are effective in approximately 20% of patients, the remaining experience limited clinical benefit and are exposed to potential adverse effects and financial costs. Clinically approved biomarkers, such as tumor mutational burden (TMB), have a modest predictive value in HNSCC.METHODS We analyzed clinical and genomic features, generated using whole-exome sequencing, in 133 ICB-treated patients with R/M HNSCC, of whom 69 had virus-associated and 64 had non-virus-associated tumors.RESULTS Hierarchical clustering of genomic data revealed 6 molecular subtypes characterized by a wide range of objective response rates and survival after ICB therapy. The prognostic importance of these 6 subtypes was validated in an external cohort. A random forest-based predictive model, using several clinical and genomic features, predicted progression-free survival (PFS), overall survival (OS), and response with greater accuracy than did a model based on TMB alone. Recursive partitioning analysis identified 3 features (systemic inflammatory response index, TMB, and smoking signature) that classified patients into risk groups with accurate discrimination of PFS and OS.CONCLUSION These findings shed light on the immunogenomic characteristics of HNSCC tumors that drive differential responses to ICB and identify a clinical-genomic classifier that outperformed the current clinically approved biomarker of TMB. This validated predictive tool may help with clinical risk stratification in patients with R/M HNSCC for whom ICB is being considered.FUNDING Fundación Alfonso Martín Escudero, NIH R01 DE027738, US Department of Defense CA210784, The Geoffrey Beene Cancer Research Center, The MSKCC Population Science Research Program, the Jayme Flowers Fund, the Sebastian Nativo Fund, and the NIH/NCI Cancer Center Support Grant P30 CA008748.

Subjects

Subjects :
Immunology
Oncology
Medicine

Details

Language :
English
ISSN :
15588238
Volume :
133
Issue :
19
Database :
Directory of Open Access Journals
Journal :
The Journal of Clinical Investigation
Publication Type :
Academic Journal
Accession number :
edsdoj.3ed24c58f7546a1a3e8b395d5a3c618
Document Type :
article
Full Text :
https://doi.org/10.1172/JCI169823