Progression of coronary artery calcification in melanoma patients treated with immune checkpoint inhibitors assessed on routine non-gated CT scans
N Laachir, E Kapiteijn, J W Jukema, M L AntoniAbstract
Background/introduction
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. However, ICIs are associated with immune-related adverse events. While early reports primarily focused on myocarditis, accumulating evidence indicates an increased risk of cardiovascular disease. Inflammation-driven acceleration of atherosclerosis has been proposed as a potential underlying mechanism. Despite its clinical relevance, the progression of coronary artery calcification (CAC) in this patient population has not been fully characterized, particularly when assessed using routine imaging.
Purpose
This study aimed to evaluate longitudinal changes in CAC as a marker of atherosclerosis in melanoma patients treated with immune checkpoint inhibitors.
Methods
A retrospective cohort study was performed including patients with stage III and IV melanoma treated with immune checkpoint inhibitors between 2012 and 2024, who underwent serial CT imaging during treatment follow-up. CAC was assessed using a visual ordinal scoring system at baseline and at 1-year and 2-year follow-up. Changes in CAC severity over time were evaluated using paired Wilcoxon signed-rank tests and an ordinal mixed-effects model. In addition, the proportion of patients demonstrating CAC progression was calculated for each follow-up time.
Results
95 patients were included of whom 93 and 62 underwent CT imaging at 1 year and 2 year follow-up, respectively. At baseline 53.7% of patients exhibited calcifications. At 1-year follow-up, there was a significant increase in patients (60.9%) showing calcifications. At 2-years follow-up, 62.9% of the patients showed coronary calcifications. The median change in CAC score was significant at both 1 year (p< 0.001) and 2 year follow-up (p<0.001). CAC progression was observed in 27.2% of patients at 1-year follow-up and in 45.2% at 2 years follow-up. The ordinal mixed-effects model showed that compared to baseline, the odds of having a higher CAC score was significantly increased at 1 year (β = 2.72, SE 0.58; p < 0.001) and further increased at 2 years (β = 5.61, SE 0.91; p < 0.001). A linear mixed model yielded similar results with an mean increase of 0.101 points at 1 year (p<0.001) and 0.20 points at 2 years (p< 0.001). At baseline, statin users exhibited significantly higher CAC scores compared to non-users (median 5 (1.25 – 7.75), p <0.001). Patients using statins showed a higher prevalence of calcifications at baseline (87.5% vs 42.3%, p <0.001). Despite these baseline differences, there was no significant difference in CAC progression between statin users and non-users at 1 year (OR=1.49, p = 0.435) or 2 years (OR= 2.94, p = 0.096).
Conclusion
Melanoma patients treated with ICI showed an significant increase in coronary calcifications during 1 and 2 years follow-up. Simple CAC scoring can be used to identify CAC severity and progression in coronary calcifications assessed on routine non-gated CT scans.CT images of patient Changes in total CAC score