Nivolumab-Induced Myocarditis Concomitant with Myasthenia Gravis

Abstract

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. Her initial symptoms were general malaise and double vision. However, her myocarditis deteriorated rapidly the following day, necessitating a temporary pacemaker and noninvasive positive pressure ventilation in the intensive care unit. Immunohistochemical examination of a myocardial biopsy suggested an immune response on the basis of HLA associations. The patient also developed impaired adduction of her left eye and elevated serum levels of acetylcholine receptor antibody, suggesting the onset of MG. Her condition gradually improved after immediate methylprednisolone pulse therapy. 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.

Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action

“…The first specific report of myocarditis during treatment with a PD‐1/PD‐L1 inhibitor was published in 2014 [27], and a number of cases of ICI‐associated myocarditis have been described since . In an early analysis of more than 20,000 patients treated with ICIs, either alone or in combination, the incidence of myocarditis was 0.09%; the incidence of fatal myocarditis in this sample was 0.03% .…”

“…There are no universally accepted criteria for a diagnosis of ICI‐associated myocarditis, but position statements and clinical practice guidelines for myocarditis due to other causes provide benchmarks. Inexpensive and widely available tests used for diagnosing ICI‐associated myocarditis include troponin measurements and electrocardiograms . However, these tests lack the sensitivity and specificity for a definitive myocarditis diagnosis.…”

“…Additional standard imaging methods that have been used for the assessment and diagnosis of ICI‐associated myocarditis include echocardiography and cardiac magnetic resonance imaging, which may reveal left‐ventricular ejection fraction abnormalities, wall motion abnormalities, myocardial edema, and fibrosis. Even endomyocardial biopsy, currently considered the gold‐standard method for diagnosis, has its limitations, as ICI‐associated myocarditis may occur as a patchy distribution of T‐cell‐predominant lymphocytic infiltrate within or adjacent to regions of myocardial necrosis , similar to histologic findings in patients with cardiac transplant rejection . Therefore, proper diagnosis of ICI‐associated myocarditis may involve a combination of high clinical acumen, biomarkers, cardiac imaging, and endomyocardial biopsy.…”

“…Like most irAEs, which typically emerge early in the course of treatment , preliminary observations suggest ICI‐associated myocarditis generally occurs within 3 months of treatment initiation . Management of ICI‐associated myocarditis varies in published reports but frequently includes administration of corticosteroids , with outcomes ranging from complete resolution to the occurrence of major adverse cardiac events and/or death.…”

“…The basic pathophysiology of ICI‐associated myocarditis requires further elucidation. Existing data indicate myocarditis is characterized by intense infiltration of T lymphocytes and macrophages . Preliminary evidence suggests common high‐frequency T‐cell receptor sequences in infiltrates from the cardiac muscle and tumor, raising the possibility of a common (shared) epitope between the tumor and the heart .…”