Pathological findings of myocardial biopsy. Serological and in situ analyses for cardiotropic viruses were negative. Moreover, immunohistochemistry demonstrated CD8 and CD4 T cells within the myocardial tissue, as well as expression of HLA-ABC and HLA-DR antigens on the myocardial cells, suggesting an immune response on the basis of HLA associations (Fig. Pathological examination of a myocardial biopsy demonstrated lymphocytic and neutrophilic infiltrations, interstitial edema, and myocardial necrosis. She gradually improved under these supportive-care measures and continued steroid therapy, and the pacemaker was removed on the 7th hospital day. She showed decreased blood pressure with complete atrioventricular block and multifocal premature ventricular contractions on electrocardiography, and a temporary cardiac pacemaker was therefore implanted simultaneously. On the 2nd hospital day, the patient suddenly complained of dyspnea due to congestive heart failure, requiring temporary noninvasive positive pressure ventilation in the intensive care unit. After myocardial biopsy, pulse methylprednisolone was initiated at a dose of 1,000 mg for 3 days followed by 1 mg/kg/day. We therefore suspected immune-related myocarditis induced by nivolumab. Emergent coronary angiography and left ventriculography showed no abnormalities, thus excluding possible myocardial infarction. She had no typical symptoms of angina pectoris, and ultrasound cardiography demonstrated good left ventricular ejection fraction with no segmental hypokynesis or pericardial effusion. On the 1st hospital day, diffuse ST segment elevation was found on electrocardiography, and her serum creatine kinase level was 1,156 U/L (normal range 41–153 U/L), with concurrent elevation of creatine kinase-MB isoenzyme and troponin I levels. She complained of general malaise and double vision 1 week after her 3rd cycle of nivolumab administration and was subsequently admitted to our hospital because of progressive worsening of her symptoms. Case ReportĪ 69-year-old female patient, Eastern Cooperative Oncology Group performance status 2, with no history of autoimmune disorders, was treated with nivolumab as 3rd-line therapy for advanced lung adenocarcinoma with pleural dissemination and asymptomatic brain metastases. Here, we report on a patient with advanced lung cancer who developed fulminant myocarditis concurrent with myasthenia gravis (MG) following nivolumab administration. However, despite their clinical benefits, these antibodies may induce immune-related adverse events. The treatment of patients with advanced lung cancer has been changed by the introduction of immune checkpoint inhibitors such as nivolumab and pembrolizumab, known as anti-programmed cell death-1 monoclonal antibodies.
This case of nivolumab-induced “Herzmyasthenie” highlights the need to be aware that fulminant myocarditis might occur at the same time as MG during treatment with anti-programmed cell death-1 monoclonal antibodies. Her condition gradually improved after immediate methylprednisolone pulse therapy. The patient also developed impaired adduction of her left eye and elevated serum levels of acetylcholine receptor antibody, suggesting the onset of MG. Immunohistochemical examination of a myocardial biopsy suggested an immune response on the basis of HLA associations.
However, her myocarditis deteriorated rapidly the following day, necessitating a temporary pacemaker and noninvasive positive pressure ventilation in the intensive care unit. Her initial symptoms were general malaise and double vision. We report a 69-year-old female patient with advanced lung cancer who developed myocarditis concomitant with myasthenia gravis (MG), also known as “Herzmyasthenie,” after 3 cycles of nivolumab administration.
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