Immune Checkpoint Inhibitors and CVD Risk in Patients With Melanoma

Immune checkpoint inhibitor (ICI) therapy may increase the risk for major atherosclerotic cardiovascular events in patient with high-risk or advanced melanoma, study data published in Cardio-Oncology indicates.

This retrospective cohort study enrolled patients who presented with melanoma stage II, III, or IV to an academic tertiary hospital in Victoria, Australia from 2015 through 2020. Demographic and clinical data were extracted from patients’ medical records. The exposure variable of interest was ICI treatment. The outcome of interest was any major atherosclerotic cardiovascular event (MACE), including acute myocardial infarction, ischemic stroke, acute limb ischemia, and coronary or other arterial revascularization procedure. Potential MACE events were identified from imaging reports, hospital discharge summaries, or cause of death certificates. Cox proportional hazard models were used to characterize the relationship between ICI treatment and risk of MACE. Models were adjusted for demographic and clinical covariates, including prior use of certain gene inhibition therapies.

The study cohort comprised 646 patients with melanoma, of whom 289 had been treated with ICI. Baseline demographic characteristics were comparable between treatment groups; median age was 67.9 years in the ICI treated group and 66.1 years in the non-ICI treated group. Men comprised a greater percentage of the ICI group than the non-ICI group (72.0% vs 62.5%; P =.01). Melanoma characteristics, including cancer stage and histologic subtype, were also similar between patient groups.

A total of 29 cardiovascular events were observed in 23 patients, including 22 events in the ICI group. The incidence of MACE was higher in the ICI vs non-ICI group (3.6 vs 0.9 events per 100 person-years). In models adjusted for age, sex, smoking history, and previous exposure to BRAF and/or MEK inhibitors, ICI treatment was associated with an increased risk for MACE (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.1-6.9; P =.03). Among patients with a past history of MACE, ICI treatment conferred particularly elevated risk for MACE (HR, 14.4; 95% CI, 1.9-112.3; P =.01).

Results from this study suggest to investigators that ICI treatment for advanced melanoma may increase the risk for MACE, particularly in patients with a history of cardiovascular events. As study limitations, investigators cited the small number of observed MACE events; further study in a larger cohort is necessary to better investigate the risk associated with ICI.

“Our real world study confirms an association between major atherosclerotic cardiovascular events and ICI treatment in a population of high-risk and advanced melanoma patients,” study authors wrote. “As such, melanoma clinicians should consider risk factor modification and/or cardiovascular screening prior to ICI commencement in these individuals.”

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.