Immune-related adverse events predict responses to PD-1 blockade immunotherapy in hepatocellular carcinoma
Immune-related adverse events predict responses to PD-1 blockade immunotherapy in hepatocellular carcinoma
复制标题
免疫相关不良事件可预测肝细胞癌对 PD-1 阻断免疫疗法的反应
DOI：
10.1002/ijc.33609
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发表时间：
2021-05-05
影响因子：
6.4
通讯作者：
Cai, Muyan
中科院分区：
文献类型：
--
作者：
Lu, Lianghe;Xing, Kaili;Cai, Muyan
免疫检查点阻断在肝细胞癌（HCC）中显示出显著的疗效，但也通常伴随着免疫相关不良事件（irAEs）。然而，irAEs与HCC患者抗肿瘤疗效之间的关系尚不清楚。分析2018年7月至2019年11月所有接受抗pd -1抗体治疗的HCC患者，并根据其irAEs状态分为不同组。共纳入101例HCC患者，其中21例（20.8%）出现irAEs（irAEs(+)）。不良事件中，皮疹（n = 9, 8.9%）是最常见的，其次是粘膜炎（n = 3, 3.0%）和甲状腺炎（n = 3, 3.0%）。irAEs（+）组患者肿瘤有效率高于irAEs（-）组（总有效率：28.6% vs 6.3%, P = 0.011；疾病控制率：85.7% vs 60.0%, P = 0.028）。irAEs（+）组的中位无进展生存期（PFS）为14.8个月，irAEs（-）组的中位PFS为4.1个月（P < 0.001）。根据有无皮疹进一步分析，irAEs(+)/皮疹（+）组患者的PFS优于irAEs(+)/皮疹（-）组和irAEs（-）组（均P < 0.05）。多因素分析显示，irAEs是PFS的独立预后因素（危险比[HR]: 0.22, P = 0.002）。因此，irae的发生，尤其是皮疹，与PFS的显著改善有关。对irae的认识可能有助于对HCC患者的亚型进行分类，抗pd -1抗体对患者的生存有前所未有的好处。
Immune checkpoint blockade has demonstrated remarkable efficacy in hepatocellular carcinoma (HCC) but is also commonly accompanied by immune-related adverse events (irAEs). However, the association between irAEs and antitumor efficacy in HCC patients remains unknown. All patients with HCC treated with anti-PD-1 antibodies from July 2018 to November 2019 were analyzed and divided into different groups according to their irAEs' status. In total, 101 HCC patients, including 21 (20.8%) patients who presented with irAEs (irAEs(+)), were enrolled. Among the adverse events, rash (n = 9, 8.9%) was the most frequent irAE, followed by mucositis (n = 3, 3.0%) and thyroiditis (n = 3, 3.0%). Patients in the irAEs(+) group showed a higher tumor response rate than those in the irAEs(-) group (overall response rate: 28.6% vs 6.3%, P = .011; disease control rate: 85.7% vs 60.0%, P = .028). The median progression-free survival (PFS) times were 14.8 months in the irAEs(+) group and 4.1 months in the irAEs(-) group (P < .001). Further analysis based on the presence or absence of rash showed that the PFS of the patients in the irAEs(+)/rash(+) group was better than that of those in the irAEs(+)/rash(-) or irAEs(-) group (all P < .05). Multivariate analysis showed that irAEs were an independent prognostic factor for PFS (hazard ratio [HR]: 0.22, P = .002). Thus, the occurrence of irAEs, especially rash, was associated with markedly improved PFS. Awareness of irAEs may help classify the subtype of HCC patients with an unprecedented survival benefit from anti-PD-1 antibodies.