[Clinical predictive value of PD-1/PD-L1-induced electrocardiogram changes for cardiotoxicity]

Objective: 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. Methods: 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. Results: 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 (P＞0.05), while the incidence of adverse cardiac events increased after immunotherapy in group B (P＜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 (P＜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 (P＞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. Conclusions: 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.