Vasbinder Alexi, Chen YeeAnn, Procureur Adrien, Gradone Allison, Azam Tariq U, Perry Daniel, Shadid Husam, Anderson Elizabeth, Catalan Tonimarie, Blakely Pennelope, Nelapudi Namratha, Fardous Mohamad, Bretagne Marie C, Adie Sarah K, Pogue Kristen T, Leja Monika, Yentz Sarah, Schneider Bryan, Fecher Leslie A, Lao Christopher D, Salem Joe-Elie, Hayek Salim S
Division of Cardiology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
JACC CardioOncol. 2022 Dec 20;4(5):689-700. doi: 10.1016/j.jaccao.2022.11.004. eCollection 2022 Dec.
Myocarditis is a dreaded and unpredictable complication of immune checkpoint inhibitors (ICI). We sought to determine whether routinely measured biomarkers could be helpful in monitoring for ICI myocarditis.
The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes.
We conducted an observational cohort study of adults who received at least one dose of ICI at Michigan Medicine between June 2014 and December 2021 and underwent systematic serial testing for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase during ICI therapy.
Among 2,606 patients (mean age 64 ± 13 years; 60.7% men), 27 (1.0%) were diagnosed with ICI myocarditis. At diagnosis, patients with myocarditis had an elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and lactate dehydrogenase (92.6%). Findings were confirmed in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. A total of 95% of patients with ICI myocarditis had elevations in at least 3 biomarkers compared with 5% of patients without myocarditis. Among the noncardiac biomarkers, only CPK was associated (per 100% increase) with the development of myocarditis (HR: 1.83; 95% CI: 1.59-2.10) and all-cause mortality (HR: 1.10; 95% CI: 1.01-1.20) in multivariable analysis. Elevations in CPK had a sensitivity of 99% and specificity of 23% for identifying myocarditis.
ICI myocarditis is associated with changes in AST, ALT, and CPK. An increase in noncardiac biomarkers during ICI treatment, notably CPK, should prompt further evaluation for ICI myocarditis.
心肌炎是免疫检查点抑制剂（ICI）可怕且不可预测的并发症。我们试图确定常规检测的生物标志物是否有助于监测ICI相关性心肌炎。
作者研究了接受ICI治疗患者的生物标志物变化趋势及其与ICI相关性心肌炎发病率和预后的关系。
我们对2014年6月至2021年12月期间在密歇根医学中心接受至少一剂ICI治疗的成年人进行了一项观察性队列研究，并在ICI治疗期间对天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、肌酸磷酸激酶（CPK）和乳酸脱氢酶进行了系统的系列检测。
在2606例患者（平均年龄64±13岁；60.7%为男性）中，27例（1.0%）被诊断为ICI相关性心肌炎。诊断时，心肌炎患者的高敏肌钙蛋白T（100%）、ALT（88.9%）、AST（85.2%）、CPK（88.9%）和乳酸脱氢酶（92.6%）升高。在一个由30例经活检证实为ICI相关性心肌炎的独立队列中，这些结果得到了证实。与无心肌炎患者的5%相比，95%的ICI相关性心肌炎患者至少有3种生物标志物升高。在非心脏生物标志物中，多变量分析显示只有CPK与心肌炎的发生（每增加100%）（风险比：1.83；95%置信区间：1.59 - 2.10）和全因死亡率（风险比：1.10；95%置信区间：1.01 - 1.20）相关。CPK升高对识别心肌炎的敏感性为99%，特异性为23%。
ICI相关性心肌炎与AST、ALT和CPK的变化有关。ICI治疗期间非心脏生物标志物升高，尤其是CPK升高，应促使对ICI相关性心肌炎进行进一步评估。
