Faubry Clara, Faure Maxime, Toublanc Anne-Claire, Veillon Rémi, Lemaître Anne-Iris, Vergnenègre Charlotte, Cochet Hubert, Khan Sadia, Raherison Chantal, Dos Santos Pierre, Zysman Maeva
Pulmonary Department, Centre Hospitalier Universitaire (CHU) Haut-Lévèque, Bordeaux, France.
Heart Failure Unit, Cardiology Department, Centre Hospitalier Universitaire (CHU) Haut-Lévèque, Bordeaux, France.
Front Cardiovasc Med. 2022 Jun 6;9:878211. doi: 10.3389/fcvm.2022.878211. eCollection 2022.
Immune checkpoint inhibitors (ICIs) are widely used in lung cancer management. However, myocarditis, which is a rare, yet potentially severe adverse-related event associated with ICIs, could be under-reported.
This study is aimed to prospectively evaluate the cumulative incidence rate of myocarditis, through systematic screening, among patients receiving ICIs for lung cancer.
All patients who received the first administration of ICIs for non-small cell (NSCLC) and small cell lung cancer (SCLC), between May and November 2020, in the pulmonary department of Bordeaux University Hospital, were included. Echocardiography (ECG), troponin-I, and natriuretic peptide dosages before ICIs' first administration and before each infusion were recorded. ECG and magnetic resonance imaging (MRI) were done additionally, in case of at least three times increase in troponin levels, ECG modifications, and the onset of cardiovascular symptoms. Second, if possible, coronarography than endomyocardial biopsy was assessed. The primary outcome was defined as ICIs related to myocarditis onset, while secondary outcomes included other cardiovascular events, disease-free, and overall survival.
During the period of interest, 99 patients received their first infusion of ICIs for lung cancer (mean age 64 ± 9 years; 52 men, 67% with adenocarcinoma). Three cases of myocarditis without major adverse cardiac events (MACEs) occurred (two definite and one possible), and the mean duration between the first ICIs' administration and myocarditis onset was 144 ± 3 days. Median disease-free survival and overall survival were 169 [102; 233] days and 209 [147; 249] days, respectively.
In our study, systematic screening of myocarditis associated with ICIs leads to a more frequent incidence and a later onset than previously reported. None of them were severe. Additional prospective evidence is needed before we could adopt routine cardiac screening in unselected patients starting ICIs; however, these data shed new light on the risk of myocarditis associated with ICIs administration.
免疫检查点抑制剂(ICIs)在肺癌治疗中被广泛应用。然而,心肌炎作为一种与ICIs相关的罕见但可能严重的不良事件,其报告可能不足。
本研究旨在通过系统筛查,前瞻性评估接受ICIs治疗肺癌患者中心肌炎的累积发病率。
纳入2020年5月至11月间在波尔多大学医院肺病科首次接受ICIs治疗非小细胞(NSCLC)和小细胞肺癌(SCLC)的所有患者。记录首次给予ICIs前及每次输注前的超声心动图(ECG)、肌钙蛋白I和利钠肽剂量。若肌钙蛋白水平至少升高三倍、ECG改变及出现心血管症状,则额外进行ECG和磁共振成像(MRI)检查。其次,若可能,评估冠状动脉造影而非心内膜心肌活检。主要结局定义为与心肌炎发病相关的ICIs,次要结局包括其他心血管事件、无病生存期和总生存期。
在研究期间,99例患者首次接受ICIs治疗肺癌(平均年龄64±9岁;52例男性,67%为腺癌)。发生3例无严重心脏不良事件(MACEs)的心肌炎(2例确诊,1例可能),首次给予ICIs至心肌炎发病的平均时间为144±3天。无病生存期和总生存期的中位数分别为169[102;233]天和209[147;249]天。
在我们的研究中,对与ICIs相关的心肌炎进行系统筛查导致发病率比先前报道的更高且发病时间更晚。所有病例均不严重。在未选择的开始使用ICIs的患者中采用常规心脏筛查之前,还需要更多前瞻性证据;然而,这些数据为与ICIs给药相关的心肌炎风险提供了新的线索。