Assessment of coronary artery calcification progression on standard non-gated CT scans in melanoma patients treated with immune checkpoint inhibitors

Background

Immune checkpoint inhibitors (ICIs) have improved the outcomes of patients with advanced melanoma. However, ICIs are linked to a range of immune related adverse events. Furthermore, growing evidence is suggesting that ICIs may also contribute to acceleration of atherosclerosis. Despite the potential clinical implications, the evolution of coronary artery calcification (CAC) in this population remains poorly defined, particularly when evaluated on routinely acquired imaging studies.

Purpose

This study aimed to investigate changes over time in CAC as an indicator for atherosclerotic progression in melanoma patients treated with ICIs.

Methods

A retrospective cohort study was conducted including patients with stage III and IV melanoma who received ICIs between 2012 and 2024 and underwent serial CT imaging during their follow-up. CAC was graded using the visual ordinal scoring system at baseline, 1 year and 2 years after the treatment was initiated. Changes in CAC was analyzed using the paired Wilcoxon signed-rank test. Additionally, the percentage of patients exhibiting CAC progression was determined for each follow-up time point. The effect of statin use was assessed by comparing the proportions of patients demonstrating progression between statin users and non-users using Fisher’s exact test.

Results

A total of 118 patients were included, with 116 and 82 undergoing CT imaging at 1- and 2-year follow-up, respectively. The mean age was 62.1 years and 53.4% were male. Majority of patients (n=95, 80.5%) had stage IV melanoma, and 56.7% were initially treated with ipilimumab plus nivolumab. At baseline, 46.7% had no coronary artery calcifications, decreasing to 40.5% at 1 year (p=0.0233) and 36.6% at 2 years (p=0.023). The number of patients transitioning from no calcifications to calcifications was identical at both time points (n = 7). The median change in CAC score was significant at both 1-year (p < 0.001) and 2-year follow-up (p < 0.001). At 1 year, 26.7% of patients demonstrated CAC progression, increasing to 42.7% at 2 years.

At baseline, 27 patients (22.9%) were receiving statin therapy. Statin users had significantly higher baseline CAC scores (median 4 [IQR 1–7]) compared with non-users (median 0 [IQR 0–2], p < 0.001). At 1 year follow-up, 37.0% of statin users demonstrated CAC progression compared to 23.6% of non-users (p = 0.2145). At 2 years, 59.1% of statin users showed progression versus 36.7% of non-users (p=0.082).

Conclusion

Melanoma patients treated with ICIs showed a significant increase in coronary artery calcification during 1- and 2-year follow-up. Statin therapy was not associated with reduced CAC progression. Routine non-gated CT scans with simple CAC scoring may facilitate identification of calcification burden and progression.Changes in total CAC score