van den Berg Pieter F, Bracun Valentina, Noordman Michel, van der Meer Peter, Shi Canxia, Oosting Sjoukje F, Aboumsallem Joseph Pierre, de Wit Sanne, Meijers Wouter C, Jalving Mathilde, van Kruchten Michel, de Boer Rudolf A
Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands.
Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands.
JACC Adv. 2024 Nov 7;3(12):101375. doi: 10.1016/j.jacadv.2024.101375. eCollection 2024 Dec.
Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer. However, immune-related adverse events are prevalent in patients receiving ICI therapy. A serious immune-related adverse event is ICI-myocarditis, which is complex to diagnose given that the significance of early symptoms and biomarker trajectories, such as high-sensitivity troponin T (hs-TnT) are unclear.
The purpose of the study was to evaluate kinetics of hs-TnT in cancer patients receiving ICI and to identify patients at risk of developing ICI-myocarditis.
This prospective, observational, single-center study included 164 patients receiving ICI therapy. Patients' history, demographics, and clinical characteristics, as well as survival statistics, were collected from electronic patient records and used to analyze associations between elevated hs-TnT (≥14 ng/L) and a significant rise in hs-TnT (100% rise from baseline, with an absolute value ≥2x upper limit of normal (ie, ≥28 ng/L) with ICI-myocarditis.
We included 164 patients with a mean follow-up time of 1.60 ± 0.91 years. Melanoma was the most common type of cancer in the patient population, and most patients received treatment with programmed cell death protein 1 (PD-1). Twenty-six patients (16%) exhibited significant hs-TnT elevations, while 8 patients (5%) developed ICI-myocarditis. In 18 of 26 (69%) patients, ICI-myocarditis could not be diagnosed with certainty, while 10 of 26 (38%) patients had no other signs of symptoms of cardiac damage. All 8 myocarditis cases were preceded by significantly higher hs-TnT elevations than asymptomatic patients. Despite a high ICI-myocarditis incidence in our study population, cardiac mortality remained low (4%).
Significant hs-TnT elevations occur more often than previously reported, are often asymptomatic, and do not always lead to myocarditis diagnosis.
免疫检查点抑制剂（ICIs）在癌症治疗中的应用日益广泛。然而，接受ICI治疗的患者中免疫相关不良事件很常见。一种严重的免疫相关不良事件是ICI相关性心肌炎，鉴于早期症状和生物标志物轨迹（如高敏肌钙蛋白T（hs-TnT））的意义尚不清楚，其诊断较为复杂。
本研究旨在评估接受ICI治疗的癌症患者hs-TnT的动力学变化，并识别有发生ICI相关性心肌炎风险的患者。
这项前瞻性、观察性、单中心研究纳入了164例接受ICI治疗的患者。从电子病历中收集患者的病史、人口统计学和临床特征以及生存统计数据，用于分析hs-TnT升高（≥14 ng/L）和hs-TnT显著升高（较基线升高100%，绝对值≥正常上限的2倍，即≥28 ng/L）与ICI相关性心肌炎之间的关联。
我们纳入了164例患者，平均随访时间为1.60±0.91年。黑色素瘤是患者群体中最常见的癌症类型，大多数患者接受程序性细胞死亡蛋白1（PD-1）治疗。26例（16%）患者出现hs-TnT显著升高，8例（5%）患者发生ICI相关性心肌炎。26例患者中有18例（69%）无法确诊为ICI相关性心肌炎，26例患者中有10例（38%）没有其他心脏损伤的症状体征。所有8例心肌炎病例的hs-TnT升高均显著高于无症状患者。尽管我们研究人群中ICI相关性心肌炎的发病率较高，但心脏死亡率仍然较低（为4%）。
hs-TnT显著升高的情况比之前报道的更为常见，通常无症状，且并不总是导致心肌炎的诊断。
