Immune Checkpoint Inhibitor-Induced Myasthenia Gravis

Abstract

The development of immune checkpoint inhibitors (ICIs) has been a major breakthrough in cancer immunotherapy. The increasing use of ICIs has led to the discovery of a broad spectrum of immune-related adverse events (irAEs). Immune-related myasthenia gravis (irMG) is a rare but life-threatening irAE. In this review, the clinical presentations of irMG are described and the risk of irMG-related mortality is examined using information from relevant studies. In 47 reported cases of irMG with clear causes of mortality, irMG appeared to be a distinct category of neuromuscular disorders and differed from classical MG in terms of its demographic patient characteristics, pathogenesis, serology profile, response to treatment, associated complications, and prognosis. Because of the high mortality of irMG, measures to increase the vigilance of medical teams are necessary to ensure the timely identification of the signs of irMG and early treatment, particularly in the early course of ICI therapy. The diagnostic plans should be comprehensive and include the evaluation of other organ systems, such as the dermatological, gastrointestinal, respiratory, neuromuscular, and cardiovascular systems, in addition to the traditional diagnostic tests for MG. Treatment plans should be individualized on the basis of the extent of organ involvement and clinical severity. Additional therapeutic studies on irMG in the future are required to minimize irAE-related mortality and increase the safety of patients with cancer in the ICI era.

Durvalumab-induced myocarditis, myositis, and myasthenia gravis: a case report

“…Thus, given the time course of symptoms, ICI-related MG is the more likely diagnosis. Compared with classical myasthenia gravis, which has a bimodal age distribution and female predominance, MG associated with immune checkpoint inhibitors seems to occur mostly in men, at a relatively older onset [ 6 ]. Two pathogenic autoantibodies are present in the majority of MG patients: 85% have anti-acetylcholine receptor autoantibodies (AchR), and 8% have anti-muscle-specific tyrosine kinase (MuSK) autoantibodies [ 7 ].…”

Benefit and danger from immunotherapy in myasthenia gravis

“…Around 75% of these patients were positive for AChR Abs. A single patient with MuSK Abs has been reported so far [11]. From our literature review, de novo MG during ICI treatment was diagnosed so far in 9 patients treated with anti-CTLA-4, in 50 receiving PD1 or PD1-L inhibitors and in 9 under combined therapy.…”

“…MG onset or deterioration generally occurred in the early phase of ICI treatment. Symptom severity was variable, with around 10% of cases with ocular or mild generalized MG and the great majority of patients rapidly progressing to moderate-severe symptoms [11,72].…”

“…Therefore, early diagnosis, close clinical monitoring, and prompt treatment are crucial. Most patients improved with aggressive treatment that included high-dose steroids, PLEX, or IVIg [11,63,73]. Rituximab can be used in patients unresponsive to first-line therapy [63].…”

“…Moreover, several biological targeting therapies for other immune-related disorders have been associated with the worsening or the onset of MG [8][9][10]. Most recently, immunotherapy for cancer by checkpoint inhibitors, which break off the immune system blocking cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) binding to their receptors, has been associated with several immune-related adverse events including MG onset [11]. The present review is focused on the benefit and danger of the emerging therapy for MG and on possible related effects caused by immunotherapy.…”