癌症患者发生免疫相关不良反应后再次使用免疫检查点抑制剂的安全性和疗效：系统评价和荟萃分析。
Safety and Efficacy of the Rechallenge of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer: A Systemic Review and Meta-Analysis.
机构信息
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.
出版信息
Front Immunol. 2021 Sep 27;12:730320. doi: 10.3389/fimmu.2021.730320. eCollection 2021.
INTRODUCTION
Little evidence exists on the safety and efficacy of the rechallenge of immune checkpoint inhibitors (ICIs) after immune-related adverse events (irAEs) in patients with cancer.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane for articles on ICI rechallenge after irAEs for systemic review and meta-analysis. The outcomes included the incidence and associated factors for safety and objective response rate (ORR) and disease control rate (DCR) for efficacy.
RESULTS
A total of 789 ICI rechallenge cases from 18 cohort studies, 5 case series studies, and 54 case reports were included. The pooled incidence of all-grade and high-grade irAEs after rechallenge in patients with cancer was 34.2% and 11.7%, respectively. Compared with initial ICI treatment, rechallenge showed a higher incidence for all-grade irAEs (OR, 3.81; 95% CI, 2.15-6.74; < 0.0001), but similar incidence for high-grade irAEs ( > 0.05). Types of initial irAEs (pneumonitis and global irAEs) and cancer (non-small cell lung cancer and multiple cancer) recapitulated these findings. Gastrointestinal irAEs and time interval between initial irAEs and ICI rechallenge were associated with higher recurrence of high-grade irAEs ( < 0.05), whereas initial anti-PD-1/PD-L1 antibodies were associated with a lower recurrence ( < 0.05). Anti-PD-1/PD-L1 antibodies rechallenge was associated with a lower all-grade irAE recurrence ( < 0.05). The pooled ORR and DCR after rechallenge were 43.1% and 71.9%, respectively, showing no significant difference compared with initial ICI treatment ( > 0.05).
CONCLUSIONS
ICI rechallenge after irAEs showed lower safety and similar efficacy outcomes compared with initial ICI treatment.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42020191405.
简介
在癌症患者发生免疫相关不良事件（irAEs）后，免疫检查点抑制剂（ICIs）再次使用的安全性和疗效证据有限。
方法
我们在 PubMed、Web of Science、Embase 和 Cochrane 中检索了有关 irAEs 后再次使用 ICI 的系统评价和荟萃分析的文章。结局包括安全性的发生率和相关因素以及客观缓解率（ORR）和疾病控制率（DCR）的疗效。
结果
共纳入 18 项队列研究、5 项病例系列研究和 54 份病例报告的 789 例 ICI 再挑战病例。癌症患者再次使用 ICI 后发生所有级别和高级别 irAEs 的累积发生率分别为 34.2%和 11.7%。与初始 ICI 治疗相比，再挑战时所有级别 irAEs 的发生率更高（OR，3.81；95%CI，2.15-6.74； < 0.0001），但高级别 irAEs 的发生率相似（>0.05）。初始 irAEs 的类型（肺炎和全身 irAEs）和癌症（非小细胞肺癌和多种癌症）也证实了这一发现。胃肠道 irAEs 和初始 irAEs 与 ICI 再挑战之间的时间间隔与高级别 irAEs 的更高复发率相关（<0.05），而初始抗 PD-1/PD-L1 抗体与较低的复发率相关（<0.05）。抗 PD-1/PD-L1 抗体再挑战与较低的所有级别 irAE 复发率相关（<0.05）。再挑战后的 ORR 和 DCR 分别为 43.1%和 71.9%，与初始 ICI 治疗相比无显著差异（>0.05）。
结论
与初始 ICI 治疗相比，irAEs 后再次使用 ICI 显示出较低的安全性和相似的疗效结果。
系统评价注册
PROSPERO，标识符 CRD42020191405。
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