# Early-Onset Immune Checkpoint Inhibitor-Induced Myasthenia Gravis Following First-Cycle Pembrolizumab: Diagnostic Challenges and Management Strategies

## TL;DR

This paper discusses a rare case of myasthenia gravis caused by pembrolizumab, highlighting the challenges in diagnosis and the importance of early treatment.

## Contribution

The paper presents a case study emphasizing early recognition and management of ICI-induced myasthenia gravis.

## Key findings

- Early-onset myasthenia gravis can occur after first-cycle pembrolizumab treatment.
- High-dose corticosteroids and IVIG led to marked clinical improvement in the patient.
- Diagnosis of ICI-induced MG often requires clinical judgment due to lack of serological markers.

## Abstract

Immune checkpoint inhibitors (ICIs), such as pembrolizumab, represent a novel and effective class of immunotherapy in cancer treatment. However, their use is associated with potentially life-threatening immune-related adverse events; the underlying mechanisms of these negative effects remain incompletely understood. Recently, certain ICIs have been associated with the onset of myasthenia gravis (MG), which is considered a spontaneous autoimmune disorder. Due to the rarity of this presentation, there is a significant risk of delayed or missed diagnosis, which may lead to increased morbidity and mortality. This study aims to identify key clinical features, diagnostic challenges, prognostic factors, and the critical importance of early diagnosis approaches that can facilitate the timely detection of ICI-induced MG, potentially reducing the associated morbidity and mortality. A 74-year-old male with renal cell carcinoma, recently started on pembrolizumab, presented with clinical features suggestive of MG with electrophysiological evidence of mild myopathy, though definitive myositis could not be confirmed. The diagnosis was confirmed after a thorough examination and investigation. High-dose corticosteroids and intravenous immunoglobulin (IVIG) were administered, with close respiratory monitoring and symptomatic support. The patient demonstrated marked improvement in strength, swallowing, and forced vital capacity (FVC) with clinical stabilization prior to discharge, while elevated creatine kinase (7,523 U/L) and troponin (297 ng/L) suggested concurrent muscle and possible cardiac involvement, though definitive myositis and myocarditis could not be confirmed without advanced imaging or biopsy. This case illustrates the diagnostic challenges of ICI-induced MG (IrMG), particularly in the absence of positive serological markers, necessitating a clinical diagnosis based on the temporal relationship and therapeutic response. Early recognition and aggressive immunosuppressive treatment with corticosteroids and IVIG achieved excellent functional recovery, emphasizing the importance of high clinical suspicion for prompt management. While permanent pembrolizumab discontinuation was necessary due to the severity of the condition, this case highlights considerations for future rechallenge protocols under careful monitoring.