Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report

Abstract

Malignant mesothelioma is an aggressive cancer associated with prior exposure to asbestos and dismal prognosis. Immune checkpoint inhibitor therapy is currently approved by the Food and Drug Administration for pre-treated malignant pleural mesothelioma. We describe a 75-year-old patient with disseminated, progressive malignant mesothelioma receiving 2 cycles of pembrolizumab who presented with generalized muscle weakness, shortness of breath, double vision and ptosis. There was no previous history of cardiovascular disease. The clinical picture, supported by the detection of anti-titin autoantibodies suggested myasthenia gravis (MG). Also, cardiac biomarkers were elevated. Echocardiography showed new severely reduced ejection fraction. A 12-lead resting electrocardiogram (ECG) revealed ST segment elevation in the posterior leads with polymorphic ventricular extrasystoles. Because cardiac catheterization revealed no relevant coronary lesions, immune checkpoint inhibitor-associated myocarditis and MG were suspected. Management and Outcome: The patient was started on steroids. Within a few days of presentation respiratory failure set in and the patient was intubated. Recurrent arrhythmias followed, which were treated by repeated emergency electrical cardioversion. In order to relieve myasthenic symptoms, plasma exchange was initiated and 10 cycles were carried out. This consequently also led to an improvement of myocarditis. Upon discharge, the ejection fraction recovered. The patient recovered and was alive at 1-year follow-up, without relevant limitations to his quality of life. Discussion and Conclusion: The article further discusses the use of plasma exchange for immune checkpoint inhibitor-associated myocarditis based on a review of literature. We conclude that patients showing no improvement after steroid therapy for immune checkpoint inhibitor-related myocarditis should be evaluated for plasma exchange, which appears to be an effective treatment option.

Keywords: Mesothelioma; immune check inhibition; myocarditis; plasma exchange; treatment related toxicity.

Figure 1

12-lead resting electrocardiogram (ECG) prior to immunotherapy (A), showing unremarkable findings with supraventricular extrasystoles. ECG upon hospital admission (B) revealing ST segment elevation in the posterior leads with polymorphic ventricular extrasystoles. ECG upon discharge from our intensive care unit (C).

Figure 2

Coronary angiogram showing normal coronary arteries without evidence of relevant coronary artery disease. (A) left coronary artery. (B) Right coronary artery.

Figure 3

Clinical course of a 75-year-old man with myocarditis and myasthenia gravis after administration of pembrolizumab. Creatinine kinase and creatinine kinase-myocardial band activity were increased after the second dose of pembrolizumab. 1, first dose of pembrolizumab; 2, second dose of pembrolizumab; #, hospital admission; *, discharge.