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 Alnemri, Thomas Jefferson UniversityFollow
Sruti Tekumalla, Thomas Jefferson UniversityFollow
Annie Moroco, Thomas Jefferson UniversityFollow
Ioannis Vathiotis, Thomas Jefferson University
Madalina Tuluc, Thomas Jefferson UniversityFollow
Stacey Gargano, Thomas Jefferson UniversityFollow
Tingting Zhan, Thomas Jefferson UniversityFollow
David Cognetti, Thomas Jefferson UniversityFollow
Joseph Curry, Thomas Jefferson UniversityFollow
Athanassios Argiris, Thomas Jefferson UniversityFollow
Alban Linnenbach, Thomas Jefferson UniversityFollow
Andrew South, Thomas Jefferson UniversityFollow
Larry Harshyne, Thomas Jefferson UniversityFollow
Jennifer Johnson, Thomas Jefferson UniversityFollow
Adam Luginbuhl, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

6-1-2024

Comments

This article is the author's final published version in Cancer Medicine, Volume 13, Issue 11, June 2024, Article number e7370.

The published version is available at https://doi.org/10.1002/cam4.7370.

Copyright © 2024 The Author(s)

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.

Recommended Citation

Alnemri, Angela; Tekumalla, Sruti; Moroco, Annie; Vathiotis, Ioannis; Tuluc, Madalina; Gargano, Stacey; Zhan, Tingting; Cognetti, David; Curry, Joseph; Argiris, Athanassios; Linnenbach, Alban; South, Andrew; Harshyne, Larry; Johnson, Jennifer; and Luginbuhl, Adam, "Predictive Capacity of Immune-Related Adverse Events and Cytokine Profiling in Neoadjuvant Immune Checkpoint Inhibitor Trials for Head and Neck Squamous Cell Carcinoma" (2024). Department of Otolaryngology - Head and Neck Surgery Faculty Papers. Paper 76.
https://jdc.jefferson.edu/otofp/76

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

38847087

Language

English