Association Between Clinical Factors and Result of Immune Checkpoint Inhibitor Related Myasthenia Gravis: A Single Center Experience and Systematic Review

Abstract

BackgroundNeurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase use of ICIs, incidence of nirAEs is growing, among which ICI related MG (irMG) is causing high fatality rate. Given the limited evidence, data from a large cohort of patients with irMG is needed to aid in recognition and management of this fatal complication.ObjectiveThis study aimed to summarize clinical characteristics of irMG and explore predictors of irMG clinical outcome.MethodsWe summarized our institution's patients who were diagnosed as irMG between Sep 2019 and Oct 2021. We systematically reviewed the literature through Oct 2021 to identify all similar reported patients who met inclusion criteria. As the control group, patients with idiopathic MG were used. We collected data on clinical features, management, and outcomes of both irMG and idioMG cases. Further statistical analysis was conducted.ResultsSixty three irMG patients and 380 idioMG patients were included in the final analysis. For irMG patients, six were from our institution while the rest 57 were from reported cases. The average age of irMG patients is 70.16 years old. Forty three were male. Average time from first ICI injection to symptom onset was 5.500 weeks. Eleven patients had a past history of MG. Higher MGFA classification and higher QMGS rates were observed in irMG patients compared to idioMG patients. For complication, more irMG patients had myositis or myocarditis overlapping compared to idioMG patients. The most commonly used treatment was corticosteroids for both idioMG and irMG. Twenty one patients (35%) with irMG had unfavorable disease outcome. Single variate and multivariate binary logistic regression proved that association with myocarditis, high MGFA classification or QMGS rates at first visit were negatively related to disease outcome in irMG patients.ConclusionirMG is a life-threatening adverse event. irMG has unique clinical manifestations and clinical outcome compared to idioMG. When suspicious, early evaluation of MGFA classification, QMGS rates and myositis/myocarditis evaluation are recommended.

Myasthenia Gravis Induced by Immune Checkpoint Inhibitors: An Emerging Neurotoxicity in Neuro-Oncology Practice: Case Series

“…In recent years, some single-center case series have been published showing a cumulative incidence similar to ours. In 2018, Safa et al published the largest case series described to date, with 14 patients from the MD Anderson Center over a 7-year observation period (2011-2018) [23], followed by Shi et al [24] with six patients over two years (2019-2021) and Wong et al, with four patients [17]. At our center, we have observed an upward trend in the number of cases, which could be explained by the increasing use of these treatments.…”

Ocular Myasthenia Gravis: A Current Overview

“…[64][65][66] Therefore, the association of myasthenia with myositis in patients using PD-1 inhibitors should alert the clinicians to the risk of cardiac complications and initiate appropriate workup and aggressive immunosuppressive treatment. 67 Steroids (oral and intravenous) were the most frequent treatment (91%). Intravenous immunoglobulins and plasma exchange should be given promptly if there is a lack of steroid benefit or severe bulbar or respiratory involvement.…”

“…Intravenous immunoglobulins and plasma exchange should be given promptly if there is a lack of steroid benefit or severe bulbar or respiratory involvement. 61,67…”

Evaluation and management of acute high-grade immunotherapy-related neurotoxicity

“…As a result of immune enhancement, ICIs can exacerbate pre-existing MG [ 159 ] or cause de novo MG [ 160 ]; 75%–85% MG irAEs are new onset [ 67 , 161 ]. Myasthenia and myositis irAE overlap is well described [ 70 , 162 , 163 ]. NirAE myasthenia shows T cell infiltration in the skeletal muscle, as well as acetylcholine receptor autoantibodies [ 164 ].…”