Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease
Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease
复制标题
DOI：
10.1016/j.ejca.2017.12.008
复制
发表时间：
2018-03-01
影响因子：
8.4
通讯作者：
Lambotte, Olivier
中科院分区：
文献类型：
--
作者：
Danlos, Francois-Xavier;Voisin, Anne-Laure;Lambotte, Olivier
目的：自身免疫性或炎症性疾病（AID）患者在接受免疫检查点抑制剂（ICI）治疗时易发生免疫相关不良事件（irAE）。我们决定分析抗PD-1抗体在AID患者中的安全性和有效性，并寻找既存AID与临床结局之间的关联。方法：在一项REISAMIC登记研究中，ICI治疗患者发生≥ 2级irAE的前瞻性研究中，我们一方面研究了既存AID与无irAE生存率之间的关系，结果：我们在REISAMIC中识别了45例患者，其中53例AIDS。癌症诊断包括黑色素瘤（n = 36）、非小细胞肺癌（n = 6）和其他（n = 3）。最常见的既存艾滋病是白癜风（n = 17），银屑病（n = 12），甲状腺炎（n = 7），干燥综合征（n = 4）和类风湿性关节炎（n = 2）。20例患者（44.4%）至少发生1起irAE：其中11例与既存AID（"AID发作"）相关。20例irAE患者中有15例维持抗PD-1抗体治疗。AID患者的无IrAE生存时间（中位数：5.4个月）显著短于无AIDS患者（中位数：13个月，p = 2.1 x 10（-4））。AID组和无AID组在总生存时间和客观缓解率方面无显著差异（分别为p = 0.38和0.098）。结论：在接受抗PD-1抗体治疗的患者中，既存AID与irAE风险显著增加相关。我们的研究结果表明，使用抗PD-1抗体的癌症治疗在艾滋病患者中与在无艾滋病患者中一样有效。(C)2017爱思唯尔有限公司版权所有
Objective: Patients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome.Methods: In a prospective study of the REISAMIC registry of grade >= 2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other.Results: We identified 45 patients with 53 AIDs in REISAMIC. The cancer diagnoses included melanoma (n = 36), non-small-cell lung cancer (n = 6) and others (n = 3). The most frequent pre-existing AIDs were vitiligo (n=17), psoriasis (n=12), thyroiditis (n=7), Sjogren syndrome (n = 4) and rheumatoid arthritis (n=2). Twenty patients (44.4%) presented with at least one irAE: eleven of these were associated with a pre-existing AID ('AID flare'). Treatment with anti-PD-1 antibodies was maintained in 15 of the 20 patients with an irAE. The IrAE-free survival time was significantly shorter in AID patients (median: 5.4 months) than in AID-free patients (median: 13 months, p = 2.1 x 10(-4)). The AID and AID-free groups did not differ significantly with regard to the overall survival time and objective response rate (p = 0.38 and 0.098, respectively).Conclusion: In patients treated with anti-PD-1 antibody, pre-existing AID was associated with a significantly increased risk of irAEs. Our results indicate that cancer treatments with anti-PD-1 antibodies are just as effective in AID patients as they are in AID-free patients. (C) 2017 Elsevier Ltd. All rights reserved.