Rakshit Sagar, Molina Julian R
Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
J Thorac Dis. 2020 Nov;12(11):7032-7038. doi: 10.21037/jtd-2019-cptn-10.
Immune checkpoint inhibitors (ICIs) such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors are widely used for the treatment of multiple cancers. Seven of these agents are currently FDA approved in the US as first or second line options for solid tumors and hematologic malignancies. These agents work by downregulating pathways that suppress T-cell activation and thereby mounting an immune response to the tumor. In general, ICI are well tolerated with only mild to moderate toxicity. However, in some patients severe immune-related adverse events (irAEs) that mimic the presentation of autoimmune diseases (AID) may occur. It is believed that irAEs occur due to disruption of immunologic self-tolerance, a mechanism that also seems to explain AID. Patients with pre-existing AID are usually excluded from prospective clinical trials due to concerns for flares of the underline AID. There is limited retrospective evidence supporting the use of ICI in patients with some pre-existing AID. These patients have an increased risk of malignancy and there is an unmet need to study ICIs in this population. This manuscript intends to review the current available evidence for the safety and activity of ICIs in patients with pre-existing AID. We summarize the reported use of ICI in patients with pre-existing AID according to the primary tumor site and type of ICI used.
免疫检查点抑制剂(ICI),如细胞毒性T淋巴细胞相关蛋白4(CTLA-4)、程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡蛋白配体1(PD-L1)抑制剂,被广泛用于多种癌症的治疗。目前,其中有7种药物在美国被FDA批准作为实体瘤和血液系统恶性肿瘤的一线或二线治疗选择。这些药物通过下调抑制T细胞活化的通路来发挥作用,从而对肿瘤产生免疫反应。一般来说,ICI耐受性良好,只有轻度至中度毒性。然而,在一些患者中,可能会出现类似于自身免疫性疾病(AID)表现的严重免疫相关不良事件(irAE)。据信,irAE的发生是由于免疫自我耐受的破坏,这一机制似乎也能解释AID。由于担心潜在的AID发作,患有既往AID的患者通常被排除在前瞻性临床试验之外。支持在一些患有既往AID的患者中使用ICI的回顾性证据有限。这些患者患恶性肿瘤的风险增加,并且在这一人群中研究ICI存在未满足的需求。本手稿旨在综述目前关于ICI在患有既往AID的患者中的安全性和活性的现有证据。我们根据原发肿瘤部位和所使用的ICI类型,总结了在患有既往AID的患者中使用ICI的报道情况。