Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer

Abstract

Background: Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer.

Methods: In this case-control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI).

Results: The patients had a median age of 66 years (IQR: 58-69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression.

Conclusions: ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment.

Trial registration number: NCT04430712.

Keywords: Immune Checkpoint Inhibitors; Immunotherapy; Non-Small Cell Lung Cancer.

Conflict of interest statement

Competing interests: TGN has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, Amgen, Sanofi, Genentech, Roche, and AbbVie, outside of the current work. TGN also reports consultant fees from Bristol Myers Squibb for a Scientific Advisory Board focused on myocarditis related to immune checkpoint inhibitors. The study was funded directly by an unrestricted grant from AstraZeneca. TGN also reports research grant funding from Bristol Myers Squibb for work related to immune checkpoint inhibitors. BF reports unrelated grant support from MedImmune/AstraZeneca and MedTrace, as well as grants from NIH/NHLBI outside the submitted work. JT reports speaker’s bureau Siemens Healthcare GmbH and speakers bureau Bayer AG, reviewer Universimed Cross Media Content GmbH, and consultant Core Lab Black Forrest GmbH, all unrelated to this work.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Central Figure. Aortic atherosclerotic plaque progression in patients with lung cancer over time. Schematic aortic plaque cross-sectional drawings: yellow represents non-calcified plaque volume and bright blue hexagonals represent calcium.