Cardiotoxicity of Contemporary Anticancer Immunotherapy

Abstract

Purpose of review Contemporary anticancer immunotherapy, particularly immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell therapy, has changed the landscape of treatment for patients with a variety of malignancies who historically had a poor prognosis. However, both immune checkpoint inhibitors and CAR T cell therapy are associated with serious cardiovascular adverse effects. As immunotherapy evolves to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of its associated cardiotoxicity will be even higher. Recent findings ICI can cause myocarditis, which usually occurs early after initiation, can be fulminant, and prompt treatment with high-dose corticosteroids is crucial. CAR T cell therapy frequently leads to cytokine release syndrome, which is associated with cardiomyopathy or arrhythmia development and may also result in circulatory collapse. Supportive treatment, as well as tocilizumab, an anti-interleukin-6 receptor antibody, is the cornerstone of treatment. Recent findings suggest that preexisting cardiovascular risk factors and disease may increase the risk of such cardiotoxicity, and prompt recognition, as well as treatment, may favorably alter the outcomes. Summary ICI and CAR T cell therapy have improved cancer-related outcomes; however, they both are associated with potentially therapy-limiting cardiotoxicity. Cardio-oncologists are required to play an important role in patient selection, pretherapy cardiovascular optimization, and prompt recognition and treatment of cardiotoxicity.

Cardiotoxicity Associated with Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Recognition, Risk Factors, and Management

“…Prior to CAR-T infusion, patients with pre-existing systolic and diastolic dysfunction should be volume optimized and monitored closely during infusion due to the risk for fluid shifts [35]. In addition, outpatient medications should be reviewed, particularly antihypertensives, antiplatelets, and other anticoagulants given the risk of hemodynamic compromise after CAR-T infusion as well as cytopenias due to lymphodepletion (Figure 2) [35,37].…”

“…If hypotension or tachycardia develops, patients should undergo volume resuscitation. However, close attention should be paid to symptoms of vascular leak and pulmonary edema [37]. If refractory to fluid boluses, transfer to the ICU for close hemodynamic monitoring and vasopressor initiation should be considered.…”

“…In hypotension, initial treatment with intravenous crystalloids is recommended [35]. Close clinical monitoring to diagnose refractory hypotension and acute fluid shifts predisposing to capillary leak and respiratory failure is important [37]. Patients with refractory hypotension should be initiated on vasopressor support and monitored closely in the ICU.…”

“…Alvi et al reported that in patients with troponemia following CAR-T infusion, the risk of a cardiovascular event increases with each 12-h delay in administration of tocilizumab [31]. It is generally accepted to start tocilizumab in the presence of hemodynamic instability requiring vasopressor support, increasing oxygen requirement and/or evidence of end-organ dysfunction (unstable arrhythmia, myocardial infarction, cardiomyopathy) [35,37,43].…”

“…An alternative IL-6 inhibitor, siltuximab, has also been used in CRS. Its mechanism differs to that of tocilizumab in that is directly binds to circulating IL-6 [37,40]. Prior studies have administered it either interchangeably with tocilizumab or as an option in refractory CRS [38].…”