Complete Atrioventricular Block Associated with Pembrolizumab-induced Acute Myocarditis: The Need for Close Cardiac Monitoring

Abstract

Pembrolizumab, a humanized monoclonal IgG4 antibody directed against programmed death-1, is an immune checkpoint inhibitor that has been introduced for the treatment of non-small-cell lung cancer. However, immune checkpoint inhibitors may cause severe immune-related adverse events. We herein present a case of lung cancer with complete atrioventricular block associated with acute myocarditis, which developed 16 days after the administration of pembrolizumab. The clinical course of this case suggested a strong need for close cardiac monitoring when pembrolizumab is administered on an outpatient basis.

Keywords: acute myocarditis; complete atrioventricular block; immune checkpoint inhibitors; immune-related adverse events; pembrolizumab.

Figure 1.

Electrocardiogram (ECG) at 1 month before admission (A) revealed normal sinus rhythm. ECG on admission (B) showed a complete atrioventricular block with wide QRS complexes.

Figure 2.

Echocardiography on admission revealed a preserved left ventricular systolic function, with an ejection fraction of 70% and no myocardial edema. (A) End diastole and (B) End systole.

Figure 3.

Chest X-ray on admission revealed no signs of heart failure.

Figure 4.

Coronary angiography did not reveal any significant stenosis.

Figure 5.

The histological examination of a liver biopsy specimen (Hematoxylin and Eosin staining). (A, ×40) A very low-power field. (B, ×200) Lymphocytic/lymphoplasmacytic infiltration in the portal tracts extending into the lobule. (C, ×200) An apoptotic hepatocyte can be recognized as acidophilic body (arrow), induced by cytotoxic T-cells due to immune abnormalities.

Figure 6.

Chest X-ray after pacemaker implantation.

Figure 7.

The organizational structure of the front-line immunotherapy team (FIT). The FIT members cooperated with each other to manage immune-related adverse events (irAEs).