Abstract:
Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01-1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06-1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01-1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04-1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09-1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01-1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01-1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00-1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75-0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76-0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62-0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61-0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis.
摘要:
免疫检查点抑制剂相关性心肌炎(ICIs-M)是一种罕见且高度致命的免疫相关不良事件(irAE),在常见的irAE中。本研究旨在寻找能够准确反映疾病状态和预后的循环生物标志物。根据ICIs相关心肌炎的诊断标准,纳入48例ICIs-M患者。对于所有入选的患者,从医疗系统中回顾性地提取了有价值的信息,主要包括人口统计信息,肿瘤信息和实验室检查。随访期定义为首次诊断ICIs-M后30天。在这项研究中,ICIs-M的30日死亡率为24.4%.在使用多变量分析工具调整潜在的混杂因素后,我们证明了生物标志物在预测ICIs-M患者30天死亡率方面的卓越表现,包括PLT(危险比(HR),1.07;95%置信区间(95CI),1.01-1.14;p=0.028),ALT(HR,1.23;95CI,1.06-1.41;p=0.005),AST(HR,1.06;95CI,1.01-1.10;p=0.015),LDH(HR,1.15;95CI,1.04-1.26;p=0.004),肌钙蛋白I(HR,1.44;95CI,1.09-1.89;p=0.009),PLR(血板/淋巴细胞)(HR,1.04;95%CI,1.01-1.07;p=0.024),LAR(乳酸脱氢酶/白蛋白)(HR,1.05;95CI,1.01-1.09;p=0.012),和AAR(天冬氨酸转氨酶/白蛋白)(HR,1.18;95CI,1.00-1.39;p=0.048)。对受试者工作特性的分析表明,曲线下面积(AUC)大于或等于0.80的生物标志物为LDH(截止值,724.5;AUC,0.86;95CI,0.75-0.97),LAR(截止值,18.11;AUC,0.87;95CI,0.76-0.97),肌钙蛋白I(临界值,0.87;AUC,0.80;95CI,0.62-0.99),和AAR(截止值,1.52;AUC,0.80;95CI,0.61-0.98)。LDH,LAR,肌钙蛋白I,AAR和AAR是一组有前景的生物标志物,在预测免疫相关性心肌炎30天死亡率方面表现出优异的预测能力。