Pembrolizumab-Induced Ocular Myasthenic Crisis

Our plain-English summary of Pembrolizumab-Induced Ocular Myasthenic Crisis, by C.J. Lorenzo, H. Fitzpatrick, V. Campdesuner, et al (Curēus, 2020).

The study

• Authors: C.J. Lorenzo, H. Fitzpatrick, V. Campdesuner, J. George, N. Lattanzio
• Journal: Curēus
• Published: 2020;12(7):e9192
• Type of article: Case report
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pembrolizumab, one of many novel immune checkpoint inhibitors (ICPi), is a monoclonal antibody that enhances immunity against cancer cells. Extensive escalation in immune activity predisposes to unsought immune-related adverse events. Due to progressive mesothelioma, a 67-year-old man was referred to the research unit and enrolled in a clinical trial with a cluster of differentiation (CD) 27 chemotherapeutic agent. He began crossover treatment and received just two doses of pembrolizumab, 33 and 16 days prior to admission. He subsequently presented to the emergency department with three days of acute onset severe diplopia and a drooping left eye. Acetylcholine receptor (AChR) antibodies returned positive at 13.9 nmol/L, and a diagnosis of ocular myasthenia gravis (OMG) was made. During his hospitalization, the patient was managed with methylprednisolone 80 mg intravenously daily, with conversion to prednisone 60 mg by mouth daily at time of discharge. Neuro-ophthalmology consultation was sought in the outpatient setting, and the patient was started on pyridostigmine. He was readmitted two weeks later with symptoms of progressive diffuse weakness, unsteady gait, and dysphagia, all in the setting of persistent diplopia. Intravenous immunoglobulin (IVIG) was promptly initiated, in addition to the pyridostigmine previously initiated in the outpatient setting. Unfortunately, after three IVIG treatments, the patient had experienced little improvement in his symptoms, and therefore elected hospice care. Although ICPis have revolutionized the management of a multitude of malignancies, recognition of immune-related adverse events is of critical importance.

Copyright © 2020, Lorenzo et al.

In plain English

This article was a case report about one patient. A 67-year-old man with malignant mesothelioma had received chemotherapy, including cisplatin, pemetrexed and gemcitabine, over the past 10 years. After his mesothelioma progressed, he joined a clinical trial of a new CD27 agent. He then received two doses of pembrolizumab, a drug that boosts the immune system against cancer, 33 and 16 days before he came to the emergency department with three days of severe double vision and a drooping left eye. A blood test found acetylcholine receptor antibodies at 13.9 nmol/L. Doctors diagnosed ocular myasthenia gravis, a nerve-and-muscle disorder causing weakness of the eye muscles. He was treated with steroids and later pyridostigmine. Over the following days he developed widespread weakness and an unsteady walk, and two weeks later he was readmitted with worsening weakness and trouble swallowing. After three days of intravenous immunoglobulin with little improvement, he chose hospice care. The authors concluded that the case showed an infrequent complication of pembrolizumab. The article did not discuss asbestos exposure or say where in the body the mesothelioma was.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (one patient)
• Who was studied: One 67-year-old man with malignant mesothelioma, seen at Sarasota Memorial Hospital (Sarasota, USA); site of the mesothelioma not stated
• Exposure: No asbestos exposure is reported. The exposure studied was the immune checkpoint inhibitor pembrolizumab: two doses, given 33 and 16 days before admission, as crossover treatment in a clinical trial of a novel CD27 agent. This followed 10 years of earlier chemotherapy.
• Main results:
  • In this patient, acetylcholine receptor (AChR) antibodies were positive at 13.9 nmol/L, and ocular myasthenia gravis was diagnosed
  • On examination the patient had an abduction deficit of about 25% in the right eye and 100% in the left eye, with ptosis (drooping) of the left eye
  • In hospital the patient was treated with methylprednisolone 80 mg intravenously daily, switched to prednisone 60 mg by mouth daily at discharge; pyridostigmine was started after outpatient neuro-ophthalmology consultation
  • The patient was readmitted two weeks later with worsening weakness (paresis) and trouble swallowing (dysphagia)
  • After three days of a planned five-day course of intravenous immunoglobulin (IVIG) with little improvement, the patient elected hospice care
• The authors' conclusion: The authors concluded that the case showed an infrequent complication of pembrolizumab, ocular myasthenia gravis confirmed by AChR antibody positivity, which progressed to systemic myasthenia gravis requiring corticosteroids and IVIG. They stated that recognizing immune-related adverse events is of critical importance.

Topics

Medical terms in this study, explained in our Lexicon: Pembrolizumab (Keytruda), checkpoint inhibitors, Monoclonal Antibody, Immune-Related Adverse Events, Mesothelioma, Clinical Trial, Dysphagia, Hospice.

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