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

Our plain-English summary of Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report, by S.R.I. Schiopu, L. Käsmann, U. Schönermarck, et al (Translational Lung Cancer Research, 2021).

The study

• Authors: S.R.I. Schiopu, L. Käsmann, U. Schönermarck, M. Fischereder, U. Grabmaier, F. Manapov, J. Rauch, M. Orban
• Journal: Translational Lung Cancer Research
• Published: 2021;10(2):1039-1046
• Type of article: Case report
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

2021 Translational Lung Cancer Research. All rights reserved.

In plain English

This case report described one 75-year-old man treated in Munich, Germany, for malignant epithelioid mesothelioma that began as a pleural tumor and later spread widely. The article did not describe any asbestos exposure. Shortly after his second dose of the immunotherapy drug pembrolizumab, he developed muscle weakness, shortness of breath, double vision and drooping eyelids. Tests showed a severely weakened heart with normal coronary arteries. The doctors judged the findings suggestive of drug-related heart muscle inflammation (myocarditis), together with drug-related myasthenia gravis and hepatitis. No heart biopsy or cardiac MRI was done. Despite steroids, he needed a breathing tube, and heart rhythm problems required repeated electrical cardioversion. After ten cycles of plasma exchange, the authors reported that consciousness, breathing and heart function improved. He later left hospital, had about 1 year without cancer progression, and ultimately died of respiratory failure. The authors concluded that patients not improving on steroids for this complication should be evaluated for plasma exchange, which appears to be an effective treatment option.

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), with a discussion of published literature
• Who was studied: One 75-year-old man with no previous heart disease, treated at Ludwig Maximilian University hospital in Munich, Germany. He was receiving second-line treatment for malignant epithelioid mesothelioma (a pleural tumor with relapse and later widespread disease).
• Exposure: The exposure studied was the immune checkpoint inhibitor drug pembrolizumab, 200 mg every 3 weeks, of which he received 2 cycles. The article does not describe the patient's asbestos exposure.
• Main results:
  • Shortly after the second pembrolizumab cycle, the patient developed generalized muscle weakness, shortness of breath, double vision and ptosis (drooping eyelids).
  • On admission, echocardiography showed severely reduced ejection fraction (heart pumping function), and cardiac catheterization showed no relevant coronary lesions.
  • Anti-titin autoantibodies were detected in this patient at a ratio of 3.24 (normal range under 1.00), supporting myasthenia gravis.
  • The doctors considered the findings suggestive of immune checkpoint inhibitor-associated myocarditis. They also judged that the patient had checkpoint inhibitor-associated myasthenia gravis and hepatitis.
  • Despite intravenous methylprednisolone (100 mg/day), the patient developed acute respiratory failure and was moved to intensive care 72 hours later. He was then intubated.
  • The patient developed recurrent atrial fibrillation and atrial flutter, which were treated with repeated emergency electrical cardioversion.
  • After ten cycles of plasma exchange, the patient's consciousness, breathing and heart function improved, and his ejection fraction improved to moderately reduced (45 to 50%).
  • On day 40 after the first pembrolizumab dose, recurrent ventricular arrhythmias led to reintubation. The patient then improved again.
  • Pembrolizumab was stopped. Progression-free survival was about 1 year, with Karnofsky Performance Status 70%, and ejection fraction recovered to about 50 to 55%.
  • A later CT scan showed progressive disease, and the patient ultimately died of respiratory failure.
• The authors' conclusion: The authors concluded that patients who do not improve after steroid therapy for immune checkpoint inhibitor-related myocarditis should be evaluated promptly for plasma exchange, which in their view appears to be an effective treatment option. They also called for further research.
• Limitations the authors state:
  • Myocarditis was not confirmed by endomyocardial biopsy, and cardiac MRI could not be performed.
  • The authors stated that the exact mechanisms by which plasma exchange may help remain unclear.
  • The authors noted that plasma exchange is usually only available in expert medical centers.
  • The authors noted that current knowledge of this complication comes from single case reports and small case series, and that its true incidence is unknown.

Topics

Medical terms in this study, explained in our Lexicon: Pembrolizumab (Keytruda), Malignant Mesothelioma, Prognosis, checkpoint inhibitors, Pleural Mesothelioma, Biomarker, Quality of Life.

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