Immune checkpoint inhibitor-induced myocarditis with myositis and/or myasthenia gravis overlap syndrome: A case series.
IM3OS poses a high risk of mortality and disability, necessitating prompt intervention in patients experiencing neuromuscular symptoms after immune checkpoint inhibitor treatment.
Where it sits
this study against the rest of the efpeglenatide corpusSummary and findings
This study analyzed 6 male patients with immune checkpoint inhibitor-induced myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS). The median age was 70.5 years, and symptoms developed a median of 30.5 days post-ICI initiation. The study aimed to clarify clinical features and management strategies for IM3OS.
Abstract
Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events, including myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS). This syndrome poses notable management challenges and has high mortality rates. Due to limited data, its clinical features and optimal treatment strategies remain poorly understood. The present study aims to clarify these aspects and share clinical management experiences. A total of 6 patients with IM3OS were retrospectively analyzed, collecting demographic, clinical, laboratory, electrophysiological, therapeutic and outcome data. Additionally, the relevant literature was reviewed to contextualize the findings. The 6 patients, all male, with a median age of 70.5 years (range, 63-83 years), developed symptoms a median of 30.5 days post-ICI initiation. Common symptoms included fluctuating ptosis, neck weakness, fatigue, myalgia, diplopia, dysphagia, dysarthria and limb weakness. Of the 6 patients, 3 required ventilation support. Elevated creatine kinase (CK) and cardiac troponin I (cTnI) were observed in all patients, with CK and cTnI levels decreasing rapidly post-treatment. Cardiac troponin T levels remained elevated for 3 months. Myotonic discharge and increased jitter were noted in 2 patients. Treatments included corticosteroids, intravenous immunoglobulin (IVIG), plasmapheresis and rituximab. Pyridostigmine was discontinued in 2 out of 4 patients due to severe cardiac adverse effects. Despite interventions, 2 patients died and 1 was bedridden, with only 3 showing favorable outcomes. In conclusion, IM3OS has a high fatality rate, highlighting the need for prompt intervention in ICI-treated patients with neuromuscular symptoms. Serum cTnI is a reliable cardiac injury marker, and early treatment with IVIG, plasmapheresis and high-dose methylprednisolone is recommended. Pyridostigmine should be administered with caution in patients with IM3OS, particularly in the presence of bradyarrhythmic ICI-related myocarditis. Given the high mortality and disability rates associated with IM3OS, novel biological targeted therapies such as eculizumab and efgartigimod may reduce fatal outcomes.
Background
This paper addresses the clinical features and management challenges of immune checkpoint inhibitor-induced myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS). Prior knowledge indicates that immune checkpoint inhibitors can lead to severe immune-related adverse events, but specific data on IM3OS is limited. Understanding the clinical presentation and optimal treatment strategies is crucial due to the high mortality rates associated with this syndrome.
Methods
This is a retrospective analysis of 6 male patients diagnosed with IM3OS. The study collected demographic, clinical, laboratory, electrophysiological, therapeutic, and outcome data. The median age of patients was 70.5 years, with symptoms developing a median of 30.5 days post-ICI initiation.
Results
All patients exhibited elevated creatine kinase (CK) and cardiac troponin I (cTnI) levels, which decreased rapidly post-treatment. Cardiac troponin T levels remained elevated for 3 months. Of the 6 patients, 3 required ventilation support, 2 died, and 1 was bedridden, while only 3 showed favorable outcomes.
Interpretation
The findings suggest a high fatality rate associated with IM3OS, which aligns with existing literature on severe immune-related adverse events from immune checkpoint inhibitors. The effect size regarding mortality is clinically significant, indicating the need for prompt intervention. Limitations include the small sample size and retrospective nature of the study, which may restrict the applicability of the results to broader populations.
Key findings
- Median age of patients was 70.5 years (range, 63-83 years).
- Symptoms developed a median of 30.5 days post-ICI initiation.
- Elevated creatine kinase (CK) and cardiac troponin I (cTnI) were observed in all patients.
- CK and cTnI levels decreased rapidly post-treatment.
- Cardiac troponin T levels remained elevated for 3 months.
- 2 patients died and 1 was bedridden, with only 3 showing favorable outcomes.
Limitations
- small sample size of n=6
- retrospective analysis limits data reliability
- all male participants may affect generalizability
- no long-term follow-up reported