Immune checkpoint inhibitors and cardiovascular events, real world data from Belgium

Background

Immune checkpoints are molecules that modulate the immune response. Cancer cells use these to evade detection by the immune system. In turn, immune checkpoint inhibitors (ICIs) block these molecules to enhance cytotoxic T-cell recognition against tumour antigens.

Current approved ICI’s target cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and PD- ligand 1 (PD-L1) pathways. Previous studies have shown that these checkpoints are critical negative regulators of atherosclerosis, implying that blocking them could accelerate atherosclerosis, thus potentially increasing the risk of cardiovascular events (CVEs) in cancer patients.

Aim

The aim of this study was to gain insights in the occurrence of CVEs in patients during/after ICI treatment.

Methods

Via the Intermutualistic Agency, Belgian Cancer Registry and Statbel, we obtained data on 10213 patients treated with ICI for melanoma, non-small cell lung cancer, urothelial cell carcinoma and renal cell carcinoma from 2016 (year of reimbursement in Belgium) until July 2023. Endpoints were cardiovascular medication and interventions after initiation of ICI.

Results

We observe a 5-year cumulative incidence rate of 8% for any CVEs, including cardiac death, controlling for death from other causes as competing risk. Specifically, the 5-year cumulative incidence rate of cardiac death and percutaneous coronary intervention was 4.4% (n = 422) and 2.9% (n = 254) respectively. Although the 5-year survival rate in our population is only 23%, this seems to be a significant incidence rate. Medication for diabetes, dyslipidemia and hypertension was started in 4% (n=386), 3% (n=332) and 7% (n=729) of patients, respectively, after ICI initiation.

Conclusion

CVEs are an underappreciated problem in cancer patients treated with ICI. We should therefore reconsider the often-applied conservative approach, to optimize cardiovascular outcomes in a growing population with improving cancer prognosis.CI Any cardiac intervention/death  Table 1-, 2-, 5-year incidence rates