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Article Abstract

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.

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http://dx.doi.org/10.1007/s10637-024-01421-7DOI Listing

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General Medicine, Faculty of Medicine, Oda Training Center of General Practice, Oda Municipal Hospital, Shimane University, Oda, JPN.

This is a rare case of nivolumab-induced multiorgan toxicity presenting as concurrent myocarditis and interstitial pneumonia in an 81-year-old patient with metastatic renal cell carcinoma. Immune checkpoint inhibitor (ICI)-associated myocarditis, a high-mortality immune-related adverse event (irAE), often presents with nonspecific symptoms, complicating early diagnosis, particularly when coexisting with other irAEs. In this case, the diagnosis was supported by elevated cardiac biomarkers, multimodal imaging findings (echocardiography, cardiac MRI, and coronary CT angiography), and electrocardiogram (ECG) abnormalities, including new-onset atrial fibrillation and right bundle branch block, indicative of myocardial involvement.

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Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis.

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Article Synopsis
  • Baseline assessment and regular monitoring using patient history, clinical exams, lab tests, and noninvasive imaging can help detect side effects from immune checkpoint inhibitors early.
  • The text highlights various cardiotoxic effects linked to immune checkpoint inhibitors, including conditions like pericarditis and myocarditis.
  • A case study is presented of a middle-aged man with advanced esophageal cancer who experienced acute heart failure due to nivolumab-induced cardiotoxicity, despite having no prior heart issues or significant risk factors.
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Objective: Recently, several researchers have reported the incidence of cardiac-related toxicities occurring with nivolumab (Opdivo) and pembrolizumab (Keytruda). There is still a need for balance between oncology treatment efficacy and reduction of cardiotoxicity burden in immune checkpoint inhibitor (ICI)-treated patients. Thus, the primary aim was to determine whether pembrolizumab or nivolumab would present with a greater risk for cardiotoxicity reports.

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