High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy

Abstract

Background: Cancer therapy-related cardiovascular toxicity (CTR-CVT) from immune checkpoint inhibitor (ICI) therapy is still incompletely characterized, and patients with pre-existing cardiovascular disease represent a particularly high-risk cohort. Valid parameters for risk stratification of these patients are missing. Neutrophil-to-lymphocyte ratio (NLR) has been shown to predict mortality and adverse events in other cardiovascular cohorts. The present study aims to examine the predictive capacity of NLR for risk stratification of patients particularly vulnerable for CTR-CVT under ICI therapy.

Methods: We performed an analysis of 88 cancer patients (69 ± 11 years, 25% female) with pre-existing cardiovascular disease under ICI therapy from the prospective Essen Cardio-Oncology Registry (ECoR). NLR was assessed at patient enrollment and the population was divided through receiver operator characteristic (ROC) curve analysis in patients with low (< 4.57) and high (≥ 4.57) NLR. Endpoint was the whole spectrum of CTR-CVT, according to the European guidelines on cardio-oncology. The median follow-up was 357 days (interquartile range (IQR): 150-509 days).

Results: We observed 4 cases of myocarditis, 17 cases of vascular toxicity, 3 cases of arterial hypertension, 22 cases of arrhythmia or QTc prolongation and 17 cases of cardiovascular dysfunction. NLR was associated with overall CTR-CVT by univariable Cox regression (hazard ratio (HR): 1.443; 95% confidence interval (CI) 1.082-1.925; p = 0.013). However, this association was attenuated after adjusting for further confounders.

Conclusion: NLR is moderately associated with CTR-CVT in cancer patients with pre-existing cardiovascular disease under ICI therapy. Surveillance of NLR during ICI therapy might be an effective and economically biomarker for risk stratification in these high-risk patients.

Keywords: Cancer therapy-related cardiovascular toxicity; Cardiovascular disease; Immune checkpoint inhibitor; Neutrophil-to-lymphocyte ratio.

Fig. 1

Flowchart of the study population (A). Out of 1443 patients form the EcoR registry of the University Hospital Essen, 88 cancer patients under immune checkpoint inhibitor (ICI) therapy with pre-existing cardiovascular disease were identified. The study population was further divided into patients with low (< 4.57) and high (≥ 4.57) neutrophil-to-lymphocyte-ratio (NLR) according to the receiver operator characteristic (ROC) curve analysis of NLR for prediction of cancer therapy-related cardiovascular toxicity (B). AUC, area under the curve; CI, confidence interval

Fig. 2

Kaplan–Meier cumulative event curves for overall cancer therapy-related cardiovascular toxicity (CTR-CVT) with patients separated by low (< 4.57) and high (≥ 4.57) neutrophil-to-lymphocyte ratios (NLR)