Tissue is the issue! Immune Checkpoint Inhibitor Myocarditis

Background
Immune checkpoint inhibitors (ICI) have various immune related adverse events, which includes myocarditis. ICI myocarditis is thought to stem from CD8+ T cells attacking cardiomyocyte structures expressing shared antigens (epitopes) that are also identified on tumor cells.

Methods
Retrospective chart review of patients receiving endomyocardial biopsies for suspected ICI myocarditis at the University of Texas MD Anderson Cancer between January 1, 2018 and December 15, 2018 was performed. Select biopsy specimens were evaluated for T cell subtyping and electron microscopy.

Results
There were 8 endomyocardial biopsies positive for lymphocytic infiltration of myocardium and all except 1 had myocyte necrosis; thus 7 total specimens were classified as myocarditis by the Dallas criteria. There were three cases with T cells (CD3+) having a mix of both CD4+ and CD8+. One case presented with predominantly CD68+, suggesting a macrophage or monocyte lineage. One patient presented with clinical heart failure, with maintenance of preserved left ventricular ejection fraction (LVEF) throughout the clinical course. The remaining patients had presenting symptoms related to another immune related adverse event – typically myasthenia gravis with myositis – while others were incidentally found to have myocarditis after endomyocardial biopsy had been pursued due to elevated values of high-sensitivity troponin T.

Conclusions
This case series highlights the importance of early invasive endomyocardial biopsy for accurate diagnosis of immune checkpoint inhibitor induced myocarditis. Endomyocardial biopsy allows precise determination of T cell CD markers that are prominent in each case of myocarditis, which then guides treatment selection based on the cellular composition of the tissue. Current treatment strategies for ICI myocarditis are use of broad immunosuppressants such as prednisone to combat the underlying T cell infiltration. The ability of endomyocardial biopsy to immunohistochemically quantify the T cell subtypes combined with the success seen in oncology of targeted therapies opens up the possibility of employing targeted agents to treat ICI myocarditis on a cellular-specific basis.