Immune Checkpoint Inhibitor-Associated Pericarditis

Abstract

Side effects of immune checkpoint inhibitors, termed immune-related adverse events, are relatively common, but immune checkpoint inhibitor-mediated cardiotoxicities are rare; however, they can be serious and potentially fatal. Pericarditis is an infrequent cardiac toxicity of immunotherapy and predisposing factors remain unknown. Here we report three patients with NSCLC who developed pericarditis during therapy with programmed death 1/programmed death ligand 1+/- CTLA-4 inhibitors. We review the clinical presentation of these three cases and histopathologic findings from autopsies from the first two patients and a pericardial sampling that has been obtained from a pericardial window procedure in the third patient who recovered from the pericarditis episode. We also discuss the potential mechanisms, as well as what is known about pericarditis secondary to immune-related adverse events.

Keywords: Immune-related adverse events; NSCLC; Pericarditis.

Figure 1.

A) Radiation fields for palliative right hilum radiation; 1.B and 1.C) Imaging studies by positron emission tomography, B) Pretreatment and C) after 4 cycle of therapy, with marked clinical response, for case #1

Figure 2.

A) Fibrinous pericarditis adherent to the parietal (reflected superiorly) and visceral pericardium, 2.B) Bread-loaf sections of the formalin-fixed heart showing a fibrinous, hemorrhagic exudate covering the heart and epicardial fat (green arrow). The epicardial surface is covered by a fibrinous exudate measuring 4-5mm in thickness, representing a classic “bread and butter” pericarditis.

Figure 3:

1^st, 2^nd and 3 rd row are macroscopic, H&E and TILs multiplexing images from case 1, 2 and 3 respectively. First column (3.A, 3.F) shows macroscopic images from pericardial sample for case 1, 2; Second column (3.B, 3.G and 3.K) shows H&E images of the pericardial samples x10 magnification), 3^rd column (3.C, 3.H and 3.L) is representing multiplexing with CD 3 (green), granzyme (red) and Ki 67 (blue channel); 4^th column (3.D, 3.I, 3.M)is representing multiplexing with CD4 (green), CD8 (red), CD20 (blue); 5^th column (3.E, 3.J, 3.N) is representing CD68 (green), PD-L1 (red).