The lethal M triad of myocarditis, myositis, and myasthenia gravis post immune checkpoint inhibitors therapy: A systematic review

Abstract

Background

With the widespread use of immune checkpoint inhibitors (ICIs) for cancer treatment, rare or uncommon immune-related adverse events (irAEs) are frequently being reported. As some of these irAEs can be severe or life-threatening with patients presenting to the emergency departments and acute care centers for care, understanding the presentation and management of these events is important. Here, a systematic review was conducted to examine the reported characteristics and management of myocarditis, myositis, and myasthenia gravis triad after ICI therapy.

Methods

Following PRISMA guidelines, we conducted a systematic review that included studies written in English published in PubMed and Embase up to August 1^st, 2023 that reported concurrent myocarditis, myositis, and myasthenia gravis in the setting of ICI. Data on presentation, patients’ characteristics, management, and outcomes were collected. Qualitative synthesis and descriptive statistics were used to analyze and report the main results.

Results

A total number of 61 cases with the M triad were identified, of which the majority had melanoma or lung cancer (51%) with a median age of 71 years. Almost all the patients (92%) were treated with PD-1 inhibitors. The main frequent complaints were dyspnea (50.8%), ptosis (49.2%), and diplopia (36.1%). Corticosteroids and intravenous immunoglobulin were the main treatment modalities. Twenty-one (34.4%) patients died in the hospital.

Conclusion

Concurrent M triad of myocarditis, myositis, and myasthenia gravis following ICI therapy is not uncommon and can present to the emergency department with a spectrum of complaints. As these concurrent irAEs are associated with high mortality rates, prompt recognition and thorough investigations by emergency department physicians are vital for effective management and early intervention. More research is needed to better identify risk factors that can be used as predictors to identify high-risk patients who may develop these events after ICI therapy, for which multidisciplinary collaboration and point-of-care testing in parallel with early recognition is necessary when evaluating these patients when they present to the emergency departments or acute care centers.