Immune checkpoint inhibition increases aortic inflammation on 18F-FDG PET/CT: a retrospective cohort study in patients with Merkel cell carcinoma receiving avelumab

Background Patients with cancer treated with immune checkpoint inhibitors are at increased risk of cardiovascular events. Preclinical studies suggest that this may be driven by inflammation-induced acceleration of atherosclerosis. Objective We aimed to evaluate changes in vessel wall inflammation assessed using 18F-FDG positron emission tomography/computed tomography (PET/CT) after initiation of immune checkpoint inhibitors. 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 and after 3 months of treatment. 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 the incidence of major 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 1.52 (IQR, 1.39-1.70) at baseline to 1.64 (IQR, 1.41-1.97) after 3 months of avelumab treatment (change, 7.8%; p=0.022). No significant changes in TBRmax were observed in the carotid arteries, bone marrow, and spleen. Statin use was not associated with change in TBRmax. During the median follow-up of 50 months (IQR, 32-65), one patient developed nonfatal ischemic stroke. Conclusion Treatment with avelumab was associated with an increase in 18F-FDG uptake in the descending aorta after 3 months, which supports the concept of inflammation-driven accelerated atherosclerosis in patients receiving immune checkpoint inhibitors.