Cardiac toxicity of immune-checkpoint inhibitors: a clinical case of nivolumab-induced myocarditis and review of the evidence and new challenges

Abstract

Immune checkpoint inhibitors have revolutionized cancer treatment due to their undeniable efficacy, but a range of new adverse events (AE) has emerged. In particular, cardiac toxicity is a potentially fatal AE, and introduces new challenges regarding its underlying molecular mechanisms of occurrence, optimal treatment and follow up, and prevention. We present a clinical case of a patient with advanced kidney cancer treated with nivolumab as a third line treatment. After four cycles, the patient developed nonspecific symptoms and was hospitalized, identifying a set of clinical, analytical and electrocardiographic alterations compatible with myocarditis. Despite the intensive support, the patient died and a necropsy study was performed. We present a detailed description of the clinical case including the pathological and molecular findings, and we conduct a review of the available evidence related to immune-mediated cardiac toxicity to offer some new highlights in the management of this AE.

Keywords: immune-related adverse events; kidney; myocarditis; nivolumab.

Figure 1

ECG baseline before starting nivolumab treatment: sinus rhythm at 60 bpm with isolated extrasystoles (A). ECG at myocarditis clinical onset: atrial fibrillation and left bundle branch block (B).

Figure 2

H&E section of myocardial tissue with necrotic focus containing dense lymphocytic infiltrates (A); immunohistochemistry of lymphoid component disclosing PD-1 cells (B), CD8 (C), and CD4 lymphocytes (D). 100× magnification.