Background: Rare cases of severe myocarditis are reported during treatment with nivolumab. Troponin, a biomarker of cardiac damage, is a key component of the diagnostic workup of many cardiac disorders, including myocarditis. This study investigates the role of troponin to assess cardiac involvement during nivolumab therapy for non-small cell lung cancer (NSCLC).
Materials and methods: We evaluated 59 NSCLC patients, analyzing serum samples collected within a translational research study. Troponin above the upper normal limit (0.046 ng/mL) was defined as Tn+, whereas normal but detectable troponin (0.015-0.045) was defined as Tndet. Troponin alterations were interpreted on the grounds of the following elements: peak values and time curve, cardiac comorbidities, signs and symptoms coincident to troponin elevation, ECG, echocardiography, and disease progression.
Results: No patient had cardiovascular events. Among 362 available blood samples, Tn+ (max 0.317 ng/mL) was found in 13 determinations belonging to 6 patients. Seven other patients had isolated Tndet. In five patients, Tn+ was attributed to cardiac comorbidities, disease progression, or worsening clinical status. One patient without cardiac history and in good clinical condition had a sustained troponin increase-soon after the start of therapy-and after careful evaluation of all relevant elements, it was interpreted as a marker of nivolumab-related subclinical myocarditis.
Conclusion: Tn+ may occur in NSCLC patients treated with nivolumab, but in most cases it does not indicate nivolumab cardiotoxicity. In some cases, however, a careful interpretation of troponin alteration, especially at the beginning of therapy, enables identification of subclinical myocarditis, thus allowing early cardiac treatment.
Implications for practice: Myocarditis is a rare but serious adverse event of immune checkpoint blockade with nivolumab, which needs to be recognized as soon as possible. This article suggests that troponin, a user-friendly biomarker of myocardial cytotoxicity, might be useful for early detection of immune-mediated myocarditis. However, because troponin abnormalities might also be related to a number of conditions capable of causing myocardial oxygen demand-supply mismatch, a careful cardiac assessment should be performed in non-small cell lung cancer patients in order to properly interpret any troponin increase. According to the available evidence, monitoring troponin during the first weeks of treatment can be considered reasonable.
摘要
背景. 在使用Nivolumab治疗期间报告了罕见的重症心肌炎病例。肌钙蛋白是心脏损伤的生物标志物,是诊断多种心脏疾病(包括心肌炎)的关键组成部分。本研究探讨肌钙蛋白在非小细胞肺癌(NSCLC)治疗中评估心脏受累程度所起的作用。
材料与方法.我们评估了59例NSCLC患者,分析了转化研究中采集的血清样本。高于正常上限的肌钙蛋白(0.046 ng/mL)定义为Tn+,而正常但可检测到的肌钙蛋白(0.015‐0.045)定义为 Tndet。肌钙蛋白的变化根据以下因素解释:峰值和时间曲线、心脏合并症、与肌钙蛋白升高相一致的症状和体征、ECG、超声心动图、疾病进展情况。
结果.患者未出现心血管事件。362份有效血样中,6例患者的13份血样测出Tn+(最高0.317 ng/mL)。另外7例患者仅检出Tndet。在5例患者中,Tn+被认为是心脏并发症、疾病进展或临床状况恶化所致。1例无心脏病史的患者,临床状况良好,治疗开始后不久肌钙蛋白持续升高,经仔细评估所有相关因素后,持续升高的肌钙蛋白解释为与Nivolumab相关的亚临床心肌炎的标志物。
结论.NSCLC患者使用Nivolumab治疗时可能出现Tn+,但在大多数情况下,并不代表Nivolumab有心脏毒性。然而,在某些情况下,仔细解释肌钙蛋白的变化,特别是在治疗开始时,可以识别亚临床心肌炎,从而使早期心脏治疗成为可能。
实践启示:心肌炎是一种罕见,但严重的免疫检查点阻断剂Nivolumab治疗的不良事件,需要尽快识别。本文认为肌钙蛋白是一种识别心肌细胞毒性有用的生物标志物,可用于早期发现免疫介导的心肌炎。然而,由于肌钙蛋白异常也可能与一些可能导致心肌氧供需不匹配的情况有关,因此应在非小细胞肺癌患者中仔细评估,正确解释任何肌钙蛋白增加的情况。根据现有证据,在治疗头几周监测肌钙蛋白被认为是合理的。
Keywords: Cardiotoxicity; Immunotherapy; Lung cancer; Nivolumab; Troponin.
© AlphaMed Press 2018.