Integrated Cancer Center Ghent, Department of Medical Oncology, AZ Maria Middelares, Buitenring Sint-Denijs 30, 9000, Ghent, Belgium.
Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
J Med Case Rep. 2022 Jul 14;16(1):275. doi: 10.1186/s13256-022-03487-4.
Myocarditis in patients treated with immune checkpoint inhibitors has previously been reported to be rare, though it has most likely been underreported owing to misdiagnosis in the absence of overt clinical presentation. Early detection and characterization of this potentially life-threatening immune-related adverse event is of major importance. Herein we report a case of early-onset myocarditis in an asymptomatic patient treated with dual checkpoint inhibition for metastatic cholangiocarcinoma.
A 69-year-old male Caucasian patient with metastatic cholangiocarcinoma presented with mild epigastric pain and troponinemia prior to the third dose of dual checkpoint inhibition (ipilimumab 1 mg/kg body weight and nivolumab 3 mg/kg body weight). Initial workup showed no significant abnormalities (physical/neurological examination, electrocardiogram, 72-hour Holter monitoring, and a transthoracic echocardiogram). However, cardiac magnetic resonance imaging revealed a zone of contrast enhancement in the inferior segment of the left ventricular wall indicating a recent episode of myocarditis. Despite steroid initiation (0.5 mg/kg oral prednisolone per day), troponin levels kept increasing, in the absence of coronary disease, for which steroids were increased to 1.5 mg/kg/day. Fluorodeoxyglucose positron emission tomography/computed tomography, 28 days after detecting elevated troponin levels, depicted multiple zones of active myocardial inflammation (basal septal, mid-anterior, and apical inferior). The patient is currently stable, and troponinemia is slowly decreasing while steroids are steadily being tapered.
As the number of cancers treated with immune checkpoint inhibitors is expanding, the incidence of immune checkpoint inhibitor-induced myocarditis is likely to increase. Moreover, the emerging combination of immune checkpoint inhibitors with non-immune checkpoint inhibitor therapies with potential synergistic cardiotoxic side effects (for example, tyrosine kinase inhibitors) will further complicate the diagnosis of immune-related cardiotoxicity. This case highlights the urgent need for predictive biomarkers to stratify patients at risk and to develop a standardized and multidisciplinary management approach for early diagnosis and treatment of this severe immune-related adverse event.
先前有报道称，接受免疫检查点抑制剂治疗的患者发生心肌炎较为罕见，但由于缺乏明显的临床表现，可能存在误诊，因此这种情况很可能被低估了。早期发现和描述这种可能危及生命的免疫相关不良事件非常重要。在此，我们报告一例接受双重免疫检查点抑制治疗转移性胆管癌的无症状患者发生早期心肌炎。
一名 69 岁白人男性，患有转移性胆管癌，在接受双重免疫检查点抑制（伊匹单抗 1mg/kg 体重和纳武单抗 3mg/kg 体重）的第三剂治疗前出现轻度上腹痛和肌钙蛋白血症。初步检查无明显异常（体格/神经系统检查、心电图、72 小时动态心电图监测和经胸超声心动图）。然而，心脏磁共振成像显示左心室壁下节段存在对比增强区，提示近期发生心肌炎。尽管开始使用皮质类固醇（每天 0.5mg/kg 口服泼尼松龙），但肌钙蛋白水平仍持续升高，且无冠心病，因此将皮质类固醇增加至 1.5mg/kg/天。在检测到肌钙蛋白水平升高 28 天后，氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描显示多个活跃心肌炎症区（基底隔段、中前段和下 apical 段）。目前患者病情稳定，肌钙蛋白血症缓慢下降，同时皮质类固醇逐渐减少。
随着接受免疫检查点抑制剂治疗的癌症数量不断增加，免疫检查点抑制剂引起的心肌炎的发生率可能会增加。此外，免疫检查点抑制剂与具有潜在协同心脏毒性的非免疫检查点抑制剂治疗联合使用（例如，酪氨酸激酶抑制剂）将进一步使免疫相关心脏毒性的诊断复杂化。本病例强调了迫切需要预测性生物标志物来对高危患者进行分层，并制定标准化和多学科管理方法，以早期诊断和治疗这种严重的免疫相关不良事件。
