Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

Genta, S. et al. (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42(1), 276. (doi: 10.1186/s13046-023-02851-6) (PMID:37865776) (PMCID:PMC10589949)

Abstract

Background: Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb). Methods: We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal–Wallis test. MFI 500 was used as threshold to define autoAb reactivity. Results: A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009). Conclusions: Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).

• Item Type: Articles
• Additional Information: This study was supported by Dr Spreafco’s research funding and Dr. Genta’s Novartis Young Canadian Investigator Award. Study drugs for the INSPIRE and MET4-IO studies were kindly provided by Merck and NuBiyota.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Spiliopoulou, Dr Pavlina
• Authors: Genta, S., Lajkosz, K., Yee, N. R., Spiliopoulou, P., Heirali, A., Hansen, A. R., Siu, L. L., Saibil, S., Stayner, L.-A., Yanekina, M., Sauder, M. B., Keshavarzi, S., Salawu, A., Vornicova, O., Butler, M. O., Bedard, P. L., Razak, A. R. A., Rottapel, R., Chruscinski, A., Coburn, B., and Spreafico, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Experimental and Clinical Cancer Research
• Publisher: BioMed Central
• ISSN: 1756-9966
• ISSN (Online): 1756-9966
• Copyright Holders: Copyright © The Author(s) 2023
• First Published: First published in Journal of Experimental and Clinical Cancer Research 42(1):276
• Publisher Policy: Reproduced under a Creative Commons licence