Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer

• Published in: Journal for immunotherapy of cancer Vol. 12; no. 7; p. e009278
• Main Authors: Wondergem, Niels E, Miedema, Iris H C, van de Ven, Rieneke, Zwezerijnen, Gerben J C, de Graaf, Pim, Karagozoglu, K Hakki, Hendrickx, Jan-Jaap, Eerenstein, Simone E J, Bun, Rolf J, Mulder, Dorien C, Voortman, Jens, Boellaard, Ronald, Windhorst, Albert D, Hagers, J Pascal, Peferoen, Laura A N, de Gruijl, Tanja D, Bloemena, Elisabeth, Brakenhoff, Ruud H, Leemans, C René, Menke-van der Houven van Oordt, C Willemien
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 22-07-2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adult; Aged; Alcohol; Anemia; Biomarkers; Cancer therapies; Chemotherapy; Clinical/Translational Cancer Immunotherapy; Female; Head & neck cancer; Head and Neck Cancer; Humans; Immune Checkpoint Inhibitor; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Male; Malnutrition; Metastasis; Middle Aged; Molecular Imaging - methods; Mouth Neoplasms - diagnostic imaging; Mouth Neoplasms - drug therapy; Mouth Neoplasms - pathology; Neck; Neoadjuvant; Neoadjuvant Therapy - methods; Nivolumab - pharmacology; Nivolumab - therapeutic use; Oral cancer; Original Research; Patients; Pneumonia; Positron-Emission Tomography - methods; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Radiation therapy; Squamous cell carcinoma; Surgery; Surgical outcomes; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tomography; Head and Neck Cancer; Immune Checkpoint Inhibitor; Neoadjuvant
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2024-009278

BackgroundAddition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome.MethodsIn this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included 18F-BMS-986192 (PD-L1) PET and 18F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology.ResultsGrade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8+ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1.ConclusionTogether these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations.