Xue N, Peng L L, Wu D W, Li X J
Department of Functional Examination, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2024 Oct 23;46(10):979-986. doi: 10.3760/cma.j.cn112152-20231024-00230.
To observe the electrocardiogram (ECG) changes of programmed death receptor 1 (PD-1)/programmed death receptor-ligand 1 (PD-L1) immune checkpoint inhibitors before and after immunotherapy of patients during clinical antitumor process, and to explore the occurrence and influencing factors of cardiotoxicity of immune checkpoint inhibitors. A total of 93 patients with locally advanced or metastatic solid tumors confirmed by pathological diagnosis in Cancer Hospital of Chinese Academy of Medical Sciences from October 1, 2019 to September 30, 2020 were selected and treated with PD-1/PD-L1 inhibitor monotherapy. Groups were divided according to immunotherapy regimen: Group A (drug code: 609A), 16 patients were given 1 mg/kg of the drug for 21 days; Group B (drug code: HX008), 23 patients were treated with 200mg for 21 days; Group C (drug code: GB226), 28 patients were treated with 3mg/kg for 14 days; Group D (drug code: LP002), 26 patients were treated with 900mg for 14 days. The patients were monitored and followed up for 10 cycles. The ECG results of each group were recorded, and the correlation between ECG abnormality and cardiotoxicity was analyzed. A total of 75 patients showed abnormal ECG that met the diagnostic criteria. There was no significant difference in abnormal ECG rate after immunotherapy in group A (＞0.05), while the incidence of adverse cardiac events increased after immunotherapy in group B (＜0.05), and the abnormal ECG rate increased significantly after chemotherapy in group C and group D. There was statistical difference before and after immunotherapy (＜0.001). The number of abnormal cases in group A (8 cases, 50.0%, 8/16) was significantly lower than that of group B (20 cases, 87.0%, 20/23). The number of abnormal cases in group C and group D was 24 (85.7%) and 23 (88.4%), respectively, without statistical difference (＞0.05), but their abnormal rates of ECG were higher than that in group A. The incidence of electrical adverse events in immunotherapy center of patients with underlying diseases was 1.93 times higher than that of patients without underlying diseases. The incidence of central electrical adverse events during immunotherapy in group B, C and D was 6.667, 6.000 and 7.667 times higher than that in group A, respectively. The high sensitivity of early ECG changes induced by immune checkpoint inhibitors enables early prediction of related cardiotoxicity. The presence or absence of comorbid underlying disease and drug dosage are correlated with the occurrence of adverse cardiac events, and these early changes provide a evidence for clinical treatment and prevention.
观察程序性死亡受体1（PD-1）/程序性死亡受体配体1（PD-L1）免疫检查点抑制剂在临床抗肿瘤过程中患者免疫治疗前后的心电图（ECG）变化，探讨免疫检查点抑制剂心脏毒性的发生情况及影响因素。选取2019年10月1日至2020年9月30日在中国医学科学院肿瘤医院经病理诊断确诊的93例局部晚期或转移性实体瘤患者，采用PD-1/PD-L1抑制剂单药治疗。根据免疫治疗方案分组：A组（药物代码：609A），16例患者给予1mg/kg药物，共21天；B组（药物代码：HX008），23例患者给予200mg，共21天；C组（药物代码：GB226），28例患者给予3mg/kg，共14天；D组（药物代码：LP002），26例患者给予900mg，共14天。对患者进行10个周期的监测和随访。记录各组的心电图结果，分析心电图异常与心脏毒性的相关性。共有75例患者心电图异常符合诊断标准。A组免疫治疗后心电图异常率差异无统计学意义（＞0.05），而B组免疫治疗后心脏不良事件发生率升高（＜0.05），C组和D组化疗后心电图异常率显著升高。免疫治疗前后差异有统计学意义（＜0.001）。A组异常例数（8例，50.0%，8/16）显著低于B组（20例，87.0%，20/23）。C组和D组异常例数分别为24例（85.7%）和23例（88.4%），差异无统计学意义（＞0.05），但其心电图异常率高于A组。有基础疾病患者免疫治疗中心电不良事件发生率比无基础疾病患者高1.93倍。B组、C组和D组免疫治疗期间中心电不良事件发生率分别比A组高6.667倍、6.000倍和7.667倍。免疫检查点抑制剂诱导的早期心电图变化的高敏感性能够早期预测相关心脏毒性。基础疾病的有无及药物剂量与心脏不良事件的发生相关，这些早期变化为临床治疗和预防提供了依据。
