Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity
Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity
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DOI：
10.1016/j.ejca.2016.12.038
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发表时间：
2017-04-01
影响因子：
8.4
通讯作者：
Kaehler, Katharina C.
中科院分区：
文献类型：
--
作者：
Gutzmer, Ralf;Koop, Anika;Kaehler, Katharina C.
目的：程序性细胞死亡蛋白1(PD-1)抑制剂是转移性黑色素瘤和其他肿瘤实体的常用治疗策略。患者和方法：对7个德国皮肤癌中心接受PD-LI治疗的转移性黑色素瘤患者进行了回顾性评估，研究对象为既有自身免疫性疾病的转移性黑色素瘤患者(A组，n=19)、新的、不存在的IRAE的发展以及PD-LI治疗的反应。包括2例额外的ipilimumab触发的自身免疫性结肠炎)或ipilimumab触发的IRAE(n=22，B组)。在PD-Li治疗开始时，A组有6名患者和B组有2名患者需要免疫抑制治疗。在A组，42%的患者出现先前存在的自身免疫性疾病，16%的患者出现新的IRAE。在B组，4.5%的患者出现异丙咪单抗引发的IRAE，23%的患者出现新的IRAE。所有先前存在的自身免疫性疾病或IRAE的发作都通过免疫抑制和/或对症治疗进行处理，不需要终止PD-LI治疗。肿瘤反应(A组32%，B组45%)与自身免疫的发生无关。结论：虽然先前存在的自身免疫在PD-Li治疗期间通常表现为耀斑，但由异丙咪单抗引发的IRAE的耀斑是罕见的。有效率在30%以上，与IRAE无关。PD-Li治疗可考虑用于自身免疫性疾病患者，取决于自身免疫的严重程度和活动性。(C)2017爱思唯尔有限公司。保留所有权利。
Aim: Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-li) in this patient population is limited.Patients and methods: Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-li from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-li therapy.Results: In total, 41 patients had either preexisting autoimmunity (n = 19, group A, including two patients with additional ipilimumab-triggered autoimmune colitis) or ipilimumab-triggered irAE (n = 22, group B). At PD-li therapy initiation, six patients in group A and two patients in group B required immunosuppressive therapy. In group A, a flare of preexisting autoimmune disorders was seen in 42% of patients, new irAE in 16%. In group B, 4.5% of patients showed a flare of ipilimumab-triggered irAE and 23% new irAE. All flares of preexisting autoimmune disorders or irAE were managed by immunosuppressive and/or symptomatic therapy and did not require termination of PD-li therapy. tumour responses (32% in group A and 45% in group B) were unrelated to occurrence of autoimmunity.Conclusion: While preexisting autoimmunity commonly showed a flare during PD-li therapy, a flare of ipilimumab-triggered irAE was rare. Response rates were above 30% and unrelated to irAE. PD-li therapy can be considered in patients with autoimmune disorders depending on severity and activity of autoimmunity. (C) 2017 Elsevier Ltd. All rights reserved.