Immune Checkpoint Inhibitor-Associated Cardiotoxicity in Solid Tumors: Real-World Incidence, Risk Factors, and Prognostic Analysis

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) have achieved acknowledged progress in cancer therapy. However, ICI-associated cardiotoxicity as one of the most severe adverse events is potentially life-threatening, with limited real-world studies reporting its predictive factors and prognosis. This study aimed to investigate the real-world incidence, risk factors, and prognosis of ICI-related cardiotoxicity in patients with advanced solid tumors.MethodsElectronic medical records from patients with advanced solid tumors receiving ICIs in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively reviewed. All patients were divided into the cardiotoxicity group and control group, with logistic regression analysis being implemented to identify potential risk factors of ICI-related cardiotoxicity. Furthermore, survival analysis was also performed to investigate the prognosis of patients with ICI-related cardiotoxicity.ResultsA total of 1,047 participants were enrolled in this retrospective study. The incidence of ICI-related cardiotoxicity in our hospital is 7.0%, while grade 3 and above cardiotoxicity was 2.4%. The logistic regression analysis revealed that diabetes mellitus [odds ratio (OR):1.96, 95% confidence Interval (CI): 1.05–3.65, p = 0.034] was an independent risk factor, whereas baseline lymphocyte/monocyte ratio (LMR) (OR: 0.59, 95% CI: 0.36–0.97, p = 0.037) was the protective factor of ICI-related cardiotoxicity. Survival analysis indicated that severe cardiotoxicity (≥grade 3) was significantly correlated with bleak overall survival (OS) than mild cardiotoxicity (≤grade 2) (8.3 months vs. not reached, p = 0.001). Patients with ICI-related overlap syndrome had poorer overall survival than patients with mere cardiotoxicity (9.4 vs. 24.7 months, p = 0.033). However, the occurrence of ICI-related cardiotoxicity was not significantly associated with the OS of overall population with solid tumors. Subgroup analysis showed that lung cancer and PD-L1 usage were significantly correlated with a higher incidence of severe cases.ConclusionImmune checkpoint inhibitor-related cardiotoxicity is more common in the real-world setting than the previously published studies. Diabetes mellitus and baseline LMR are the potential predictive biomarkers of ICI-related cardiotoxicity. Although ICI-related cardiotoxicity is not correlated with the prognosis of these patients in our cohort, a systematic and comprehensive baseline examination and evaluation should be performed to avoid its occurrence.