接受免疫检查点抑制剂治疗所致免疫相关不良事件与晚期原发性肝癌患者疗效的关联分析

摘要/Abstract

摘要： 目的探讨晚期原发性肝癌患者在抗PD-1/PD-L1治疗期间发生免疫相关不良事件(irAE)与疗效的相关性。方法纳入2019年1月至2022年1月接受PD-1/PD-L1抑制剂单药或联合方案治疗的晚期原发性肝癌患者80例。PD-1/PD-L1抑制剂治疗后进行疗效评估,参照常见不良反应事件评价标准CTCAE 5.0版评价免疫治疗期间irAE及其严重等级。结果 80例晚期原发性肝癌患者ICI使用特瑞普利单抗、卡瑞利珠单抗、信迪利单抗以及帕博利珠单抗治疗。在免疫治疗期间,45例(56.2%)患者出现了63次irAE,其中8例(10.0%)患者发生11次≥3级的irAE,从接受ICI治疗到irAE发生中位时间为2.4个月。常见irAE分别为反应性皮肤毛细血管增生症23次(36.5%)、皮疹/白癜风14次(22.2%)、甲状腺功能减退10次(15.9%)、肝炎6次(9.5%)、胰腺损伤3次(4.8%)、肺炎3次(4.8%)、腹泻/结肠炎2次(3.2%)、血液毒性以及神经毒性各1次(1.6%),无死亡病例。45例发生irAE的患者达到CR、PR、SD、PD分别为0例、18例(40.0%)、19例(42.2%)、8例(17.8%),未发生irAEs患者为35例,达到CR 1例(2.8%)、PR 5例(14.3%)、SD 10例(28.6%)、PD 19例(54.3%)。发生、未发生irAE患者ORR分别为40.0%(18/45)、14.3%(5/35),差异有统计学意义(P<0.05);发生、未发生irAE患者DCR分别为82.2%(37/45)、42.9%(15/35),差异有统计学意义(P<0.05)。中位随访时间为10.5个月。至随访截止,发生、未发生irAE患者中位PFS分别为10.4个月、4.3个月,差异有统计学意义(P<0.05);发生、未发生irAE患者中位OS分别为17.6个月、8.8个月,差异有统计学意义(P<0.05)。结论对于晚期原发性肝癌患者,接受PD-1/PD-L1抑制剂治疗显示出良好的疗效及安全性,同时irAE的发生与患者免疫治疗效果及临床结局之间存在相关性,是预测疗效的潜在标志物。

关键词: 晚期原发性肝癌, 免疫检查点抑制剂, 免疫相关不良事件

Abstract: Objective To explore the relationship between immune-related adverse events (irAEs) in patients with advanced primary liver cancer during anti-PD-1/PD-L1 treatment and the efficacy of immunotherapy, and to provide clinical evidence for clarifying their correlation.Methods Between January 2019 and January 2022, eighty patients with advanced primary liver cancer were treated with PD-1/PD-L1 inhibitors alone or in combination, and the included cases met the requirements. The efficacy of PD-1/PD-L1 inhibitor was evaluated after treatment, and the irAEs and its severity during immunotherapy were evaluated according to the evaluation standard of common adverse events (CTCAE version 5.0).Results The immune checkpoint inhibitors (ICIs) used in these 80 patients with advanced primary liver cancer were Tereplizumab, Karelizumab, Cindilizumab and Pabolizumab. During the immunotherapy, 45 patients (56.2%) had 63 times of irAEs, of which 8 patients (10.0%) reported 11 times of irAEs ≥3, and the median time from ICIs treatment to the present of irAEs was 2.4 months. The common irAEs were reactive cutaneous capillary hyperplasia (23 times, 36.5%), rash/vitiligo (14 times, 22.2%), hypothyroidism (10 times, 15.9%), hepatitis (6 times, 9.5%), pancreatic injury (3 times, 4.8%), pneumonia (3 times, 4.8%) and diarrhea/colitis (2 times). In 45 patients with irAEs, complete response (CR), partial response (PR), stable disease (SD) and porgressive disease (PD) were 0 (0%), 18 (40.0%), 19 (42.2%) and 8 (17.8%), respectively. In 35 patients without irAEs, CR was 1 (2.8%) and PR was 5 (14.3%). The Objective response rate (ORR) of patients with and without irAEs was 40.0% (18/45) and 14.3% (5/35) respectively, and the difference was statistically significant (P<0.05). The disease control rate (DCR) of patients with and without irAEs was 82.2% (37/45) and 42.9% (15/35) respectively, and the difference was statistically significant (P<0.05). All cases were followed up, and the median follow-up time was 10.5 months. By the end of the follow-up, the median progression-free survival (PFS) of patients with and without irAEs was 10.4 months and 4.3 months, respectively, and the difference was statistically significant (P<0.05). The median overall survival (OS) of patients with and without irAEs was 17.6 months and 8.8 months, respectively, and the difference was statistically significant (P<0.05).Conclusion For patients with advanced primary liver cancer, treatment with PD-1/PD-L1 inhibitors shows good efficacy and safety. Meanwhile, there is a correlation between the occurrence of irAEs and the efficacy and clinical outcome of immunotherapy; thus, it is a potential marker to predict the efficacy.

Key words: Advanced primary Hepatocellular carcinoma, Immune checkpoint inhibitors, Immune-related adverse events

胡志强, 门奋勇, 刘冬. 接受免疫检查点抑制剂治疗所致免疫相关不良事件与晚期原发性肝癌患者疗效的关联分析[J]. 肝脏, 2023, 28(8): 935-937.

HU Zhi-qiang, MEN Fen-yong, LIU Dong. A correlation analysis between immune-related adverse events and the curative effect caused by immune checkpoint inhibitors on patients with advanced primary Hepatocellular carcinoma[J]. Chinese Hepatolgy, 2023, 28(8): 935-937.

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