What is the clinical evidence from this study?

Study design: Cohort. Population: Cancer with pre-existing cardiovascular disease under immune checkpoint inhibitor therapy (n=88). Intervention: High neutrophil-to-lymphocyte ratio (≥ 4.57) vs. Low neutrophil-to-lymphocyte ratio (< 4.57). Primary outcome: Overall cancer therapy-related cardiovascular toxicity (CTR-CVT) (HR 1.443, 95% CI 1.082-1.925, p=0.013).

November 13, 2023Clinical Research in Cardiology26 citationsOpen Access

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

Q: What are the key findings of this study?

Higher neutrophil-to-lymphocyte ratio was associated with increased cancer therapy-related cardiovascular toxicity (HR 1.443) in patients with cardiovascular disease under immune checkpoint inhibitors.

Q: What does this research mean for the field?

A higher neutrophil-to-lymphocyte ratio is moderately associated with an increased risk of cancer therapy-related cardiovascular toxicity in cancer patients with pre-existing cardiovascular disease undergoing immune checkpoint inhibitor therapy. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

EHElias Haj‐Yehia RMRaluca Mincu SKSebastian Korste

Key Result

Higher neutrophil-to-lymphocyte ratio was associated with increased cancer therapy-related cardiovascular toxicity (HR 1.443) in patients with cardiovascular disease under immune checkpoint inhibitors.

Study Design

Type

Cohort (n=88)

Multicenter

Structured PICO

Does a high neutrophil-to-lymphocyte ratio predict cancer therapy-related cardiovascular toxicity in cancer patients with pre-existing cardiovascular disease undergoing immune checkpoint inhibitor therapy?

Population

88 cancer patients with pre-existing cardiovascular disease (e.g., coronary artery disease, congestive heart failure, peripheral or cerebral artery occlusive disease, valvular heart disease, atrial fibrillation, or history of stroke) under immune checkpoint inhibitor (ICI) therapy from the prospective Essen Cardio-Oncology Registry (ECoR). Mean age 69 ± 11 years, 25% female.

Intervention

High neutrophil-to-lymphocyte ratio (NLR ≥ 4.57) assessed at patient enrollment during immune checkpoint inhibitor therapy

Comparator

Low neutrophil-to-lymphocyte ratio (NLR < 4.57) assessed at patient enrollment during immune checkpoint inhibitor therapy

Outcome

Overall cancer therapy-related cardiovascular toxicity (CTR-CVT) according to the European guidelines on cardio-oncology (composite of CTRCD, myocarditis, vascular toxicity, new onset of arterial hypertension, and arrhythmia or QTc prolongation) at median 357 days follow-upcomposite

In cancer patients with pre-existing cardiovascular disease receiving immune checkpoint inhibitors, a high baseline neutrophil-to-lymphocyte ratio is moderately associated with an increased risk of cancer therapy-related cardiovascular toxicity.

Main Result

Effect estimate: HR 1.443 (95% CI 1.082-1.925)

p-value: p=0.013

Limitations

Cardiotoxic confounders like time interval between previous cancer therapies were not examined
Non-cardiovascular premedication apart from reported cancer treatment was not examined
No information regarding therapy with corticosteroids
Relatively small number of heterogeneous patients

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.

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