Elsevier

JACC: CardioOncology

Volume 1, Issue 2, December 2019, Pages 182-192
JACC: CardioOncology

Original Research
Immune Checkpoint Inhibitor-Related Adverse Cardiovascular Events in Patients With Lung Cancer

https://doi.org/10.1016/j.jaccao.2019.11.013Get rights and content
Under a Creative Commons license
open access

Abstract

Objectives

The purpose of this study was to evaluate whether immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE) compared with non-ICI therapies in patients with lung cancer.

Background

ICIs activate the host immune system to target cancer cells. Though uncommon, cardiovascular immune-related adverse events can be life-threatening.

Methods

A retrospective single-institution cohort study of 252 patients with pathologically confirmed lung cancer who received ICI or non-ICI therapy was analyzed. The primary endpoint was MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure.

Results

During a median follow-up of 6 months, MACE occurred in 13.3% of ICI-treated patients, with a median time to event of 51 days, compared with 10.3% and 64 days in non-ICI patients. ICIs were not associated with MACE (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.57 to 2.43; p = 0.66) in a univariable Fine-Gray regression analysis incorporating noncardiovascular death as a competing risk. Multivariable regression analyses determined that patients treated with ICIs with elevated serum troponin I >0.01 ng/ml (HR: 7.27; 95% CI: 2.72 to 19.43; p < 0.001) and B-type natriuretic peptide (BNP) >100 pg/ml (HR: 2.65; 95% CI: 1.01 to 6.92; p = 0.047) had an increased risk of MACE. Patients pre-treated or receiving combined immunotherapy with ICIs and vascular endothelial growth factor inhibitors (VEGFIs) or tyrosine kinase inhibitors (TKIs) had an increased risk of MACE (HR: 2.15; 95% CI: 1.05 to 4.37; p = 0.04).

Conclusions

ICIs were not independently associated with an increased risk of MACE in patients with lung cancer, although power is an important limitation in these analyses. ICI-associated cardiotoxicity was associated with elevations in serum troponin and BNP, and combined immunotherapy with VEGFIs or TKIs. Future studies are needed to further define the role of cardiac biomarkers as a monitoring strategy with ICI therapy.

Key Words

BNP
cardiotoxicity
immune checkpoint inhibitors
lung cancer
MACE
troponin

Abbreviations and Acronyms

BNP
B-type natriuretic peptide
CI
confidence interval
HR
hazard ratio
ICI
immune checkpoint inhibitor
IQR
interquartile range
LVEF
left ventricular ejection fraction
MACE
major adverse cardiovascular events
PD
programmed cell death protein
PD-L1
programmed cell death-ligand 1
TKI
tyrosine kinase inhibitor
TnI
troponin I
VEGFI
vascular endothelial growth factor inhibitor

Cited by (0)

Dr. Bhimaraj has been a consultant for Abbott and Abiomed. Dr. Bernicker has served on an advisory board for Guardant Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.