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Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have reshaped and have become a well-established treatment modality for multiple advanced-stage malignancies. ICIs block the immune system regulatory checkpoints, namely CTLA-4 and PD-1/PDL1, which provokes excess immune response against self-antigens. Immune modulation with ICIs can result in diverse immune-related adverse events targeting organ systems. Several cases of ICI-related cardiotoxicity were reported, while the actual incidence was likely underestimated due to heterogeneous clinical presentation. These include, but are not limited to, myocarditis, pericarditis, atherosclerosis, and arrhythmia. EKG, Troponin, Echocardiogram (TTE), and Cardiac MRI (CMRI) are indispensable diagnostic tools to aid in the management of cardiac adverse effects. Herein, we review the ICI-mediated cardiovascular adverse events, diagnosis, treatment strategies, and reintroduction of ICIs post-cardiotoxicity.

SUBMITTER: Paluri RK

PROVIDER: S-EPMC10691592 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects.

Paluri Ravi Kumar RK Pulipati Yochitha Y Regalla Dileep Kumar Reddy DKR

Oncology reviews 20231117

Immune checkpoint inhibitors (ICIs) have reshaped and have become a well-established treatment modality for multiple advanced-stage malignancies. ICIs block the immune system regulatory checkpoints, namely CTLA-4 and PD-1/PDL1, which provokes excess immune response against self-antigens. Immune modulation with ICIs can result in diverse immune-related adverse events targeting organ systems. Several cases of ICI-related cardiotoxicity were reported, while the actual incidence was likely underesti ...[more]

PMID: 38045806

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Project description:BackgroundModern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported.MethodsWe performed a retrospective analysis of the FDA Adverse Event Reporting System data of suspect product reports for immunotherapy and classical chemotherapy from January 2010-March 2020. We identified 90,740 total adverse event reports related to immune checkpoint inhibitors and classical chemotherapy.ResultsWe found that myocarditis was significantly associated with patients receiving anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1), odds ratio (OR) = 23.86 (95% confidence interval [CI] 11.76-48.42, (adjusted p-value) q < 0.001), and combination immunotherapy, OR = 7.29 (95% CI 1.03-51.89, q = 0.047). Heart failure was significantly associated in chemotherapy compared to PD-(L)1, OR = 0.50 (95% CI 0.37-0.69, q < 0.001), CTLA4, OR = 0.08 (95% CI 0.03-0.20, q < 0.001), and combination immunotherapy, OR = 0.25 (95% CI 0.13-0.48, q < 0.001). Additionally, we observe a sex-specificity towards males in cardiac adverse reports for arrhythmias, OR = 0.81 (95% CI 0.75-0.87, q < 0.001), coronary artery disease, 0.63 (95% CI 0.53-0.76, q < 0.001), myocardial infarction, OR = 0.60 (95% CI 0.53-0.67, q < 0.001), myocarditis, OR = 0.59 (95% CI 0.47-0.75, q < 0.001) and pericarditis, OR = 0.5 (95% CI 0.35-0.73, q < 0.001).ConclusionOur study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy compared to conventional chemotherapy. Understanding the clinical risk factors that predispose immunotherapy-treated cancer patients to often fatal CV adverse events will be crucial in Cardio-Oncology management.

Project description:BackgroundThere is an urgent need to better understand the diverse presentations, risk factors, and outcomes of immune checkpoint inhibitor (ICI)-associated cardiovascular toxicity. There remains a lack of consensus surrounding cardiovascular screening, risk stratification, and clinical decision-making in patients receiving ICIs.MethodsWe conducted a single center retrospective cohort study including 2165 cancer patients treated with ICIs between 2013 and 2020. The primary outcome was adverse cardiovascular events (ACE): a composite of myocardial infarction, coronary artery disease, stroke, peripheral vascular disease, arrhythmias, heart failure, valvular disease, pericardial disease, and myocarditis. Secondary outcomes included all-cause mortality and the individual components of ACE. We additionally conducted an imaging substudy examining imaging characteristics from echocardiography (echo) and cardiac magnetic resonance (CMR) imaging.ResultsIn our cohort, 44% (n = 962/2165) of patients experienced ACE. In a multivariable analysis, dual ICI therapy (hazard ratio [HR] 1.23, confidence interval [CI] 1.04-1.45), age (HR 1.01, CI 1.00-1.01), male sex (HR 1.18, CI 1.02-1.36), prior arrhythmia (HR 1.22, CI 1.03-1.43), lung cancer (HR 1.17, CI 1.01-1.37), and central nervous system (CNS) malignancy (HR 1.23, CI 1.02-1.47), were independently associated with increased ACE. ACE was independently associated with a 2.7-fold increased risk of mortality (P<0.001). Dual ICI therapy was also associated with a 2.0-fold increased risk of myo/pericarditis (P = 0.045), with myo/pericarditis being associated with a 2.9-fold increased risk of mortality (P<0.001). However, the cardiovascular risks of dual ICI therapy were offset by its mortality benefit, with dual ICI therapy being associated with a ~25% or 1.3-fold decrease in mortality. Of those with echo prior to ICI initiation, 26% (n = 115/442) had abnormal left ventricular ejection fraction or global longitudinal strain, and of those with echo after ICI initiation, 28% (n = 207/740) had abnormalities. Of those who had CMR imaging prior to ICI initiation, 43% (n = 9/21) already had left ventricular dysfunction, 50% (n = 10/20) had right ventricular dysfunction, 32% (n = 6/19) had left ventricular late gadolinium enhancement, and 9% (n = 1/11) had abnormal T2 imaging.ConclusionDual ICI therapy, prior arrhythmia, older age, lung and CNS malignancies were independently associated with an increased risk of ACE, and dual ICI therapy was also independently associated with an increased risk of myo/pericarditis, highlighting the utmost importance of cardiovascular risk factor optimization in this particularly high-risk population. Fortunately, the occurrence of myo/pericarditis was relatively uncommon, and the overall cardiovascular risks of dual ICI therapy appeared to be offset by a significant mortality benefit. The use of multimodal cardiac imaging can be helpful in stratifying risk and guiding preventative cardiovascular management in patients receiving ICIs.

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Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects.

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Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects.

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