The immune checkpoint inhibitor avelumab increases aortic inflammation on [18F]FDG PET/CT: A retrospective cohort study

BACKGROUND: Patients with cancer treated with immune checkpoint inhibitors (ICIs) are at increased risk of cardiovascular events. Preclinical studies suggest that this may result from inflammation-induced destabilization of atherosclerotic plaques.

OBJECTIVE: To evaluate changes in vessel wall inflammation assessed using [18F]FDG positron emission tomography/computed tomography (PET/CT) after ICI initiation.

METHODS: This was a single-center retrospective cohort study of patients with Merkel cell carcinoma who received at least one cycle of the programmed death ligand 1 (PD-L1) inhibitor avelumab and underwent [18F]FDG PET/CT before initiation of treatment and after 3 months. The primary outcome was the change in the target-to-background ratio (TBRmax) in the descending aorta between baseline and first follow-up scan. Secondary outcomes included the change in TBRmax in the carotid arteries, spleen, and bone marrow, and incidence of major adverse cardiovascular events.

RESULTS: Fifty-three patients were included (66% male; median age 75 years). Most patients had established risk factors for cardiovascular disease (62%). The [18F]FDG TBRmax in the descending aorta increased from 1.52 (IQR, 1.39-1.70) at baseline to 1.64 (IQR, 1.41-1.97) after 3 months of treatment (change 7.8%. p = 0.022). No significant changes were observed in the carotid arteries, bone marrow, and spleen. Statin use was not associated with an attenuated change in TBRmax. During a median follow-up of 2.3 (IQR, 1.5-4.2) years, one nonfatal ischemic stroke occurred.

CONCLUSION: Avelumab treatment was associated with an increase in [18F]FDG uptake in the descending aorta after 3 months of treatment, which may be a potential marker of inflammation-driven accelerated atherosclerosis in patients receiving ICIs.