Neutrophil-to-lymphocyte ratio and the incidence, severity, and prognosis of immune checkpoint inhibitor-related cardiotoxicities: a meta-analysis

Immune checkpoint inhibitors (ICIs) can induce immune-related cardiotoxicities (IRCs). The neutrophil-to-lymphocyte ratio (NLR) is an easily accessible inflammatory biomarker. However, its role in predicting the incidence, severity, and prognosis of IRCs remains unclear. This meta-analysis aimed to systematically evaluate the association between NLR and IRC-related outcomes in patients with cancer receiving ICIs. PubMed, Embase, Web of Science, Wanfang, and CNKI were searched for observational studies evaluating NLR in relation to IRC incidence, severity, or prognosis. Standardized mean differences (SMDs) and risk ratios (RRs), with 95% confidence intervals (CIs), were pooled using random-effects models that accounted for heterogeneity. For relative-effect analyses, hazard ratios (HRs) were treated as approximations of RRs, while odds ratios (ORs) were converted to RRs using the outcome incidence in the reference group. Ten observational studies involving 1,035 patients receiving ICIs were included. Pretreatment NLR did not differ significantly between patients with and without IRCs (3 studies; SMD = 0.07, 95% CI − 0.30 to 0.43; I² = 52%) and was not significantly associated with IRC incidence (3 studies; RR = 1.61, 95% CI 0.93–2.80; I² = 82%). In contrast, NLR measured at IRC diagnosis was significantly higher in patients with severe versus non-severe IRCs (4 studies; SMD = 0.79, 95% CI 0.50–1.08; I² = 0%) and was associated with an increased risk of severe IRCs (2 studies; RR = 1.29, 95% CI 1.11–1.50; I² = 8%). Higher NLR was also associated with poor prognosis among patients with IRCs, defined by major adverse cardiovascular events (2 studies; RR = 4.07, 95% CI 1.95–8.48; I² = 0%). Pretreatment NLR was not consistently associated with IRC incidence, whereas elevated NLR at the time of cardiotoxicity diagnosis may be associated with greater IRC severity and poorer prognosis. However, given the limited number of studies, these findings should be considered preliminary and require confirmation in larger prospective studies. PROSPERO Registration (CRD420261280410). Not applicable.