Unmasking a Rare Complication: Immune Checkpoint Inhibitors (ICIs) and Vogt-Koyanagi-Harada (VKH) Syndrome

Document Type

Conference Proceeding

Publication Date

6-1-2025

Publication Title

Journal of Clinical Oncology

Abstract

Background: ICIs have changed the paradigm of cancer treatment, but their immune-modulating effects can lead to severe immune-related adverse events (irAEs). VKH syndrome, a rare autoimmune disorder affecting pigmented tissues specifically uvea, skin, inner ear and meninges has been reported as case reports with ICIs, although real word data to elaborate on this association is limited. We aimed to assess the pharmacovigilance (PV), reporting rate, reaction outcomes of VKH syndrome using the FDA Adverse Event Reporting System (FAERS) database. Methods: We identified 309,038 ICI-treated patients. VKH syndrome was reported in 203 (0.06%) cases. The ROR for VKH syndrome was significantly elevated for ICI-exposed patients compared to patients not exposed to ICIs (n = 410, 0.002%; OR: 34.06, p < 0.0001, 95% CI: 28.7936,40.3115). ICI exposure correlated with a 34-fold increase in the rates of VKH. On further stratification of targets of ICI, our analysis revealed that there was a significant predisposition to VKH with PD1 and CTLA4 agents compared to PDL1. VKH syndrome ROR with PD1 vs PDL1 (12.4, 95% CI 5.5, 28.05) and CTLA4 vs PDL1 (16.66, 95% CI 7.2, 32.4) with p < 0.0001. Results: We identified 309,038 ICI-treated patients. VKH syndrome was reported in 203 (0.06%) cases. The ROR for VKH syndrome was significantly elevated for ICI-exposed patients (ROR 34.06, 95% CI 28.79-40.31, p < 0.0001). Compared to the FAERS database incidence of VKH (n = 410, 0.002%), there was a 34-fold increase in VKH risk with ICI exposure. Further, there was a significant predisposition to VKH with PD1 and CTLA4 agents compared to PDL1. VKH syndrome ROR with PD1 vs PDL1 (12.4, 95% CI 5.5, 28.05) and CTLA4 vs PDL1 (16.66, 95% CI 7.2, 32.4) with p < 0.0001. Conclusions: Our analysis of the FAERS data suggests a potential association between ICI use and an increased risk of VKH syndrome. Although VKH syndrome appears to be a rare irAE, clinicians should be vigilant for its manifestations in patients receiving ICIs. In this analysis we also highlighted a potential increased likelihood of VKH syndrome through CTLA4 and PD1 targeting agents compared to PDL1 targeting agents. Early recognition and prompt management are essential to mitigate potential complications and improve patient outcomes. Further research is needed to confirm this association and explore the underlying mechanisms

Volume

43

Issue

16 Suppl

First Page

e14667

Comments

2025 ASCO (American Society of Clinical Oncology) Annual Meeting, May 30 - June 3, 2025, Chicago, IL

Last Page

e14667

DOI

10.1200/JCO.2025.43.16_suppl.e14667

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