Cardiac toxicity after conventional
antineoplastic drugs (eg,
anthracyclines) has historically been a relevant issue. In addition, targeted
therapies and biological molecules can also induce
cardiotoxicity.
Immune checkpoint inhibitors are a novel class of anticancer drugs, distinct from targeted or tumour type-specific
therapies.
Cancer immunotherapy with
immune checkpoint blockers (ie,
monoclonal antibodies targeting
cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its
ligand (PD-L1)) has revolutionised the management of a wide variety of
malignancies endowed with poor prognosis. These inhibitors unleash antitumour immunity, mediate
cancer regression and improve the survival in a percentage of patients with different types of
malignancies, but can also produce a wide spectrum of immune-related adverse events. Interestingly, PD-1 and PD-L1 are expressed in rodent and human cardiomyocytes, and early animal studies have demonstrated that CTLA-4 and PD-1 deletion can cause autoimmune
myocarditis.
Cardiac toxicity has largely been underestimated in recent reviews of toxicity of checkpoint inhibitors, but during the last years several cases of
myocarditis and fatal
heart failure have been reported in patients treated with checkpoint inhibitors alone and in combination. Here we describe the mechanisms of the most prominent checkpoint inhibitors, specifically
ipilimumab (anti-CTLA-4, the godfather of checkpoint inhibitors) patient and
monoclonal antibodies targeting PD-1 (eg,
nivolumab,
pembrolizumab) and PD-L1 (eg,
atezolizumab). We also discuss what is known and what needs to be done about
cardiotoxicity of checkpoint inhibitors in patients with
cancer. Severe cardiovascular effects associated with checkpoint blockade introduce important issues for oncologists, cardiologists and immunologists.