Pembrolizumab-induced myasthenia gravis-like disorder, ocular myositis, and hepatitis: a case report

Abstract

Introduction Pembrolizumab and other immune checkpoint inhibitors are the emerging treatment for selected, high-grade malignancies. However, a small number of patients are unable to tolerate its adverse effects, leading to discontinuation of this potentially life-changing therapy. In this study, we present a case of high-grade urothelial carcinoma patient, who experienced neurocomplications during the first pembrolizumab administration. However, we were able to limit the adverse effect by concomitant use of low-dose oral steroids. Case presentation A 75-year-old Taiwanese female with high-grade urothelial carcinoma of the left ureter came to the neurology clinic with complaints of acute onset of bilateral ptosis 16 days after her first infusion of pembrolizumab. It was found that she developed complete bilateral ptosis and limited extraocular muscle movements. Myasthenia gravis-related antibodies and repetitive stimulation test were negative. We diagnosed her with pembrolizumab-induced myasthenia gravis-like disorder and myositis based on clinical symptoms and elevation of muscle enzymes. We commenced methylprednisolone pulse therapy followed by oral steroid therapy with gradual resolution of the symptoms. Three months later, the patient received a second cycle of pembrolizumab with low-dose oral steroids without any complications. Conclusion Pembrolizumab exerts its antitumor activity by interfering with the binding of programmed death 1 and its ligand, programmed death ligand 1. As a result, enhanced cytotoxic T cells can recognize tumor cells and induce cellular death. However, neurological complications may be severe and require prompt recognition and treatment. Our case demonstrated that concomitant use of low-dose steroids and pembrolizumab might prevent such complications.

Pembrolizumab-Induced Myasthenia Gravis and Myositis: Literature Review on Neurological Toxicities of Programmed Death Protein 1 Inhibitors

“…The incidence of MG as a consequence of PD-1 antagonist initiation is 30-37% according to a case series analysis [1]. Further literature review revealed that there have been similar presentations to our patient's clinical course including those with bladder cancer who developed myositis, MG and myo-carditis [7,[13][14][15][16][17][18]. The evidence highlights the possibility of certain relation between the type of malignancy and the organ or system affected by ICI, especially since iMG has been associated with concurrent myocarditis and myositis in 8% in similar cases [4,19].…”

A Case of Pembrolizumab-Induced Myasthenia Gravis

“…One study found an incidence of high-grade (Grade 3-4) irAE, including myasthenic syndromes, was less than 1% in patients receiving immune checkpoint inhibitors (ICI) [6]. Myasthenia gravis [7][8][9][10][11], encephalitis/meningitis [12], inflammatory polyradiculopathies [13] such as Guillain-Barre syndrome, and peripheral neuropathy have been described most commonly [14]. The significance of these associated neurological disorders resides in their high mortality rates.…”

Concurrent Ocular Myopathy and Myasthenia Gravis After Zimberelimab Therapy in a Patient With Non-Small-Cell Lung Cancer

“…Unlike conventional ocular myopathy, ICI-related ocular myopathy can manifest as painless ophthalmoplegia. 6 7 Although EOM muscle biopsies were not performed in our patient due to the risk of permanent disability, the clinical and MRI findings were suggestive of EOM myopathy. Anti-CV2 seropositivity can be accompanied by MG with thymoma, 8 but paraneoplastic syndrome associated with anti-CV2 antibodies is a rare condition.…”