Pembrolizumab-induced Myasthenia Gravis: Literature Review of Ocular Manifestations and a Refractory Case

Abstract

Immune checkpoint inhibition is a new and promising therapy approved for the treatment of various malignancies. Pembrolizumab is a potent tumor suppressor that acts by upregulating the immune system to recognize cancer cells which may result in disrupted self-tolerance. We describe a case and perform a literature review of myasthenia gravis with ocular manifestations after treatment with pembrolizumab. Our case had bilateral ptosis refractory to conventional treatment, and she remained functionally blind as a result. The literature review included 28 cases of immune-related myasthenia gravis, and a 30% mortality rate excluding deaths from primary cancer progression was shown. Under half had full symptom resolution (n=13, 46%), and there was no clear correlation between specific management strategies and prognosis. Patients with isolated ocular myasthenia gravis (n=9, 32%) were twice as likely to be symptom-free after treatment compared with generalized myasthenia gravis (75% vs. 39%). Respiratory involvement was associated with twice the mortality rate (60% vs. 33%) and triple the risk of noncomplete symptom resolution (20% vs. 61%). The majority of cases had their pembrolizumab discontinued (n=20, 71%), but 3 were successfully rechallenged by utilizing prophylactic low-dose steroids. Patients with immune-related myasthenia gravis experience increased mortality and morbidity but if steroid-responsive, may benefit from the reintroduction of anti–programmed cell death protein 1 therapy for end-stage malignancy with close monitoring. A high index of clinical suspicion for immune-related adverse effects are critical in an era of rising immunotherapy use.

Myasthenia Gravis Associated With Pembrolizumab for Relapsed Lung Cancer After Thymoma Resection

“…Although appropriate management, including corticosteroids, intravenous immunoglobulin, and plasmapheresis based on mechanical ventilation, yields a favorable prognosis, MG can still be life-threatening. One study on pembrolizumab reported a 30% mortality rate in patients who developed MG, and less than half of the patients achieved full symptom remission [ 7 ]. In that study, only 32% of patients with MG tested positive for AChR antibodies.…”

severe case of Pembrolizumab-induced triad of myasthenic crisis, myocarditis, and anti-SSA myositis

“…They can have severe clinical presentations, rapid clinical deterioration with long-term sequela and high mortality rates. 5 Some patients present with a triad of MG, myositis and myocarditis and seem to develop respiratory failure more frequently than those with MG alone. Most of the death from MG complications was seen in those with elevated CK levels with MG overlapping with myositis and myocarditis.…”

“…Anti-acetylcholine receptor antibodies were the most commonly found antibodies followed by anti-MuSK and anti-striated muscle antibodies in patients with overlapping MG, myocarditis and myositis. 5 However, no cases have been reported regarding the type of myositis antibodies seen in pembrolizumab-induced myositis or the triad of MG, myositis, and myocarditis. We report positive anti-SSA antibody for the first time in a patient with this triad.…”

Immune checkpoint inhibitors induced side effects of the peripheral nervous system

“…Recent knowledge of ICI-induced MG has been gained from case reports and retrospective case series as prospective trials are missing [16]. The incidence of ICI-MG is estimated to be between 0.2 and 5.0% [17]. The rate of anti-AChR positivity in pure irMG is not definitely established.…”

“…For the definite diagnosis or irMG anti-AChR (or anti-MuSK) antibody positivity and pathological electrodiagnostic studies are required [5]. As the incidence of pathognomonic antibodies can be lower than in classic MG, probable irMG can be also diagnosed after improvement with cholinesterase inhibitors [17]. It is clinically important that patients are evaluated for overlapping irMyositis and cardiomyositis.…”