# Immune-related adverse events in patients with preexisting myasthenia gravis and thymoma following immune checkpoint inhibitor treatment: a retrospective, observational study

## TL;DR

This study found that patients with preexisting myasthenia gravis and thymoma experience severe immune-related adverse events when treated with immune checkpoint inhibitors, and pretreatment immunosuppression improves outcomes.

## Contribution

The study identifies a strong association between preexisting myasthenia gravis and thymoma with severe irAEs following ICI therapy and suggests pretreatment immunosuppression improves outcomes.

## Key findings

- All MGT patients experienced grade 3 or higher irAEs and ICI-induced myocarditis.
- Pretreatment immunosuppressive therapy and combined steroid/IVIG treatment improved outcomes in MGT patients.
- Thymoma patients with germinal centers had severe irAEs, suggesting GCs as a potential biomarker.

## Abstract

Immune checkpoint inhibitors (ICIs) can induce immune system activation and cause immune-related adverse events (irAEs). This study aimed to assess the incidence and management of irAEs in thymoma patients with preexisting MG who received ICI therapy.

This was a retrospective observational cohort study. From September 2018 to May 2024, 12,916 patients received ICI therapy at our hospital. Among them, six patients with preexisting MG and thymoma (MGT) received ICI treatment, and ten thymoma patients without MG (TOMA) served as controls. irAEs, MG flares, and treatment outcomes were primarily assessed through retrospective review of medical records. Anti-acetylcholine receptor antibody (AChR-Ab) levels and pathological thymoma tissue features were analyzed to explore the potential mechanisms underlying the irAEs.

Compared with TOMA patients (n=10), all MGT patients (n=6) had grade 3 or higher irAEs (p=0.034) and experienced ICI-induced myocarditis (p=0.011). All MGT patients experienced symptom exacerbation, including a myasthenic crisis. MGT patients who received immunosuppressive agents before ICI therapy and those who received both steroids and intravenous immunoglobulin (IVIG) during irAE occurrence had better outcomes. AChR-Ab levels markedly increased one month after the onset of irAEs. Furthermore, two TOMA patients with germinal centers (GCs) in their thymus tissues had severe irAEs, whereas two without GCs had no irAEs.

In this study, irAEs were common and severe in patients with preexisting MG and thymoma following ICI therapy. Pretreatment immunosuppressive therapy was associated with better clinical outcomes. The presence of GCs in thymoma patients without MG may serve as a predictive biomarker for the occurrence of irAEs.