Cardiotoxicity associated with immune checkpoint inhibitors: Current status and future challenges

Abstract

Immune checkpoint inhibitors (ICIs) are the most notable breakthrough in tumor treatment. ICIs has been widely used in tumor patients, but its wide range of immune-related adverse events (irAEs) should not be ignored. irAEs can be involved in any organ system, including immune-related cardiotoxicity. Although the cardiotoxicity induced by immune checkpoint inhibitors is rare, it is extremely lethal and has attracted increasing attention. PD-1 and PD-L1 are expressed in human cardiomyocytes, so the application of PD-1/PDL-1 inhibitors can cause many adverse reactions to the cardiovascular system. This review summarizes the latest epidemiological evidence on the cardiovascular toxicity of programmed cell death protein-1(PD-1)/programmed cell death ligand-1(PD-L1) inhibitors and the clinical manifestations, as well as the potential pathological mechanisms. These updates may provide a novel perspective for monitoring early toxicity and establishing appropriate treatment for patients with ICI-related cardiotoxicity.

Combinatorial immune checkpoint blockade increases myocardial expression of NLRP-3 and secretion of H-FABP, NT-Pro-BNP, interleukin-1β and interleukin-6: biochemical implications in cardio-immuno-oncology

“…Although rare, ICIs-related cardiovascular events can occur in cancer patients ( 12 ). Events of inflammatory myocarditis, vasculitis and endothelitis are seen in clinical practice and some of them may be at high mortality ( 12 , 13 ). Non-viral inflammatory myocarditis is the most observed cardiotoxic event in patients on ICIs, however the frequency is extremely low (<1%) ( 14 ).…”

Durvalumab-Induced Myocarditis and Dilated Cardiomyopathy in a Patient With Non-small Cell Lung Cancer: A Diagnostic Conundrum

“…As an ICI, durvalumab causes immune-mediate adverse events (imAEs), pneumonitis, thyroid disorders, and dermatitis/rash, with diarrhea/colitis being the most common [ 4 , 5 ]. Rarely, durvalumab can be associated with cardiac imAEs, including myocarditis, pericarditis, arrhythmias, and coronary vasculitis [ 6 ]. As per Mahmood SS's multicenteric observational study, the estimated incidence of ICI-myocarditis is 1.14% [ 7 ].…”

An Uncommon Case of Myocarditis Secondary to Durvalumab Plus Tremelimumab

“…Tumor immunotherapy is an important clinical strategy for the treatment of various solid and hematological malignancies [ 1 ]. Immune checkpoint inhibitors (ICIs) are immunotherapies that boost anticancer immune responses by targeting receptors on the surface of T-lymphocytes [ 2 ]. In other words, they redirect the host immune system toward fighting off tumor cells.…”

“…Although rare, fulminant and fatal toxic effects, such as hepatitis and cardiotoxicity, have been described [ 4 ]. Cardiovascular-related events may present as arrhythmias, pericardial disease, vasculitis, myocardial infarction, and Takotsubo cardiomyopathy, with the most common being myocarditis [ 2 ]. A retrospective study of data from eight clinical centers found that the prevalence of myocarditis was 1.14% [ 5 ].…”

“…Most cases occur early, with a median time to the onset of toxicity of 30 days, usually after the first or second ICI infusion [ 7 ]. Additionally, ICI-related myocarditis can lead to cardiogenic shock, multiorgan failure, ventricular arrhythmias, and even death in severe cases [ 2 ].…”