Onset and progression of atherosclerosis in patients with melanoma treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are effective anticancer agents but significantly increase cardiovascular risk. This could be due to its potential to induce or worsen atherosclerosis. We evaluated the onset and progression of atherosclerosis during ICI treatment in patients with melanoma and investigated risk factors for substantial (>10%/year) atherosclerotic plaque growth in five segments of the arterial tree.

Methods: Onset and yearly progression of atherosclerosis were assessed in the aortic arch, descending thoracic aorta, abdominal aorta, left and right iliac arteries via CT scans performed prior to and 1 year (±3 months) after ICI therapy initiation in patients with melanoma in the adjuvant (resected melanoma) and advanced disease (irresectable stage III and stage IV) setting. The primary outcome was defined as yearly progression of maximal plaque thickness in each arterial segment. Secondary outcomes were changes in the number of plaques, incidence of arterial thrombosis (ATE), and factors associated with substantial plaque growth in the descending thoracic aorta.

Results: In total, 244 patients were included. Plaque thickness increased significantly in all aortic segments, ranging from 3.0% to 8.0% per year (all p<0.001). In 75% of included patients, substantial plaque growth in ≥1 segment occurred. Number of plaques remained identical in 64-86% of arterial segments. Three (1.2%) developed ATE within 1 year after ICI initiation. ICI combination therapy demonstrated a trend towards increased risk of substantial plaque growth compared with monotherapy (OR 2.10 (95% CI, 0.95 to 4.66; p=0.068)), whereas antihypertensive drug usage was associated with a lower risk (OR 0.48 (95% CI, 0.24 to 0.95; p=0.036)).

Conclusion: The majority of patients with melanoma experience substantial atherosclerotic plaque growth during ICI therapy. The number of plaques remained relatively stable, suggesting that ICIs could particularly affect pre-existing plaques.