Predictive Capacity of Immune-Related Adverse Events and Cytokine Profiling in Neoadjuvant Immune Checkpoint Inhibitor Trials for Head and Neck Squamous Cell Carcinoma\

Authors

Angela E Alnemri
Sruti Tekumalla
Annie E Moroco
Ioannis Vathiotis
Madalina Tuluc
Stacey Gargano
Tingting Zhan
David M Cognetti
Joseph M Curry
Athanassios Argiris
Alban Linnenbach
Andrew P South
Larry A Harshyne
Jennifer M Johnson
Adam J Luginbuhl

Publication Date

6-1-2024

Journal

Cancer Medicine

Abstract

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay.

RESULTS: Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow-up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069-6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34-10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113-0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre-treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status.

CONCLUSIONS: irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment.

Keywords

Humans, Squamous Cell Carcinoma of Head and Neck, Immune Checkpoint Inhibitors, Male, Neoadjuvant Therapy, Female, Middle Aged, Retrospective Studies, Cytokines, Aged, Head and Neck Neoplasms, Nivolumab

Comments

Supplementary Materials

PMID: 38847087