Immune checkpoint inhibitors and the risk of major atherosclerotic cardiovascular events in patients with high-risk or advanced melanoma: a retrospective cohort study

Charlie Wang; Sophia Zoungas; Mabel Yan; Rory Wolfe; Andrew Haydon; Mark Shackleton; Mark Voskoboynik; Maggie Moore; Miles C Andrews; Stephen J Nicholls; Victoria Mar

doi:10.1186/s40959-022-00149-8

Immune checkpoint inhibitors and the risk of major atherosclerotic cardiovascular events in patients with high-risk or advanced melanoma: a retrospective cohort study

Cardiooncology. 2022 Dec 2;8(1):23. doi: 10.1186/s40959-022-00149-8.

Authors

Charlie Wang^{1

2}, Sophia Zoungas³, Mabel Yan^{4

3}, Rory Wolfe³, Andrew Haydon⁵, Mark Shackleton⁵, Mark Voskoboynik^{5

6}, Maggie Moore⁵, Miles C Andrews^{5

6}, Stephen J Nicholls^{7

8}, Victoria Mar^{4

3}

Affiliations

¹ Victorian Melanoma Service, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria, 3004, Australia. [email protected].
² School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. [email protected].
³ School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁴ Victorian Melanoma Service, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria, 3004, Australia.
⁵ Department of Medical Oncology, The Alfred Hospital, Melbourne, Victoria, Australia.
⁶ Department of Medicine - Alfred, Monash University, Melbourne, Victoria, Australia.
⁷ MonashHeart, Monash Health, Clayton, Victoria, Australia.
⁸ Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Clayton, Victoria, Australia.

Abstract

Background: Immune checkpoint inhibitors (ICI) are associated with immune-mediated adverse effects, potentially involving any organ. ICI has also been associated with an increased risk of cardiovascular disease in cancer populations.

Objective: To characterize the incidence and risk of major atherosclerotic cardiovascular events associated with ICI use in a high-risk and advanced melanoma population.

Methods: We conducted a retrospective cohort study of patients with high-risk or advanced melanoma (AJCC stage II, III or IV) presenting to an academic tertiary hospital between 2015-2020. The main outcome was major atherosclerotic cardiovascular events (MACE) including acute myocardial infarction, ischemic stroke, acute limb ischemia and coronary revascularization.

Results: The study cohort consisted of 646 patients, including 289 who had been treated with ICI. The incidence of MACE was higher in the ICI treated group (3.6 vs. 0.9 events per 100-person years). After adjusting for age, sex, smoking history and prior BRAF and/or MEK inhibitor use, ICI treatment was associated with an increased risk of MACE (HR_adj 2.8, 95% CI 1.1-6.9, p = 0.03). Elevated risk was especially pronounced in patients with a past history of MACE (HR 14.4, 95% CI 1.9-112.3, p = 0.01).

Conclusion: Patients with high-risk or advanced melanoma are at an increased risk of atherosclerotic cardiovascular events following ICI treatment, particularly those with a history of cardiovascular disease.