Normandie University, University of Caen Normandy, Centre Hospitalier Universitaire (CHU) de Caen Normandie, PICARO Cardio-oncology Program, Department of Pharmacology, EA 4650, Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, Caen, France.
Hôpitaux Universitaires Paris-Est, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Service de Cardiologie, Unico, Unité de Cardio-Oncologie APHP.6, GRC Groupe de Recherche Clinique en Cardio Oncologie, Inserm 856, Université Pierre et Marie Curie, Paris, France.
JAMA Oncol. 2020 Jun 1;6(6):865-871. doi: 10.1001/jamaoncol.2020.0726.
Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE).
To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences.
DESIGN, SETTING, AND PARTICIPANTS: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included.
The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge.
A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs.
This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.
在免疫相关不良事件（irAE）后再次使用免疫检查点抑制剂（ICI）时，关于其安全性的信息有限。
确定癌症患者在 ICI 再挑战后因相同 irAE 而停止 ICI 治疗的复发率，并确定与这些复发相关的临床特征。
设计、设置和参与者：本观察性、横断面、药物警戒队列研究分析了来自世界卫生组织数据库 VigiBase 的个体病例安全报告，该数据库包含来自 130 多个国家的病例报告。从数据库创建（1967 年）到 2019 年 9 月 1 日提取病例报告。所有连续的 ICI 病例均至少有 1 种相关 irAE。
主要结局是在 ICI 再挑战后最初 irAE 的复发率。次要结局包括在信息丰富的再挑战中，与再挑战后复发相关的因素、根据 ICI 方案（抗程序性细胞死亡 1 或抗程序性细胞死亡配体 1 单药治疗、抗细胞毒性 T 淋巴细胞抗原-4 单药治疗或联合治疗）的复发率以及再挑战后发生不同 irAE 的发生率。
共确定了 24079 例与至少 1 种 ICI 相关的 irAE 病例。在这些 irAE 中，6123 例与 ICI 再挑战相关的 irAE 中有 452 例（7.4%）为信息丰富的再挑战。观察到 130 例（28.8%；95%CI，24.8-33.1）最初 irAE 的复发。在再挑战中，结肠炎（报告比值比[OR]，1.77；95%CI，1.14-2.75；P=0.01）、肝炎（报告 OR，3.38；95%CI，1.31-8.74；P=0.01）和肺炎（报告 OR，2.26；95%CI，1.18-4.32；P=0.01）与更高的复发率相关，而肾上腺事件与较低的复发率相关（报告 OR，0.33；95%CI，0.13-0.86；P=0.03）与其他 irAE 相比。
本队列研究发现，在使用相同的 ICI 进行再挑战后，因相同的 irAE 而停止 ICI 治疗的复发率为 28.8%。对于某些患者，可以考虑重新开始 ICI 治疗，同时进行适当的监测，并使用标准治疗算法来识别和治疗毒性作用。
