Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders
Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders
复制标题
DOI：
10.1200/jco.2017.77.0305
复制
发表时间：
2018-07-01
影响因子：
45.3
通讯作者：
Awad, Mark M.
中科院分区：
文献类型：
--
作者：
Leonardi, Giulia C.;Gainor, Justin F.;Awad, Mark M.
尽管程序性死亡（PD）-1通路抑制剂目前已被用于几乎所有晚期非小细胞肺癌（NSCLC）患者，但大量NSCLC合并自身免疫性疾病（AID）患者被普遍排除在免疫治疗临床试验之外。因此，PD-1和PD-配体1（PD-L1）抑制剂在NSCLC患者和潜在的AID.MethodsAs多机构的努力的一部分，我们回顾性地收集了临床病理数据，从NSCLC患者和艾滋病的历史谁接受单药治疗与PD-1或PD-L1（本文称为PD-[L]1）抑制剂。合格的艾滋病包括但不限于：风湿病，神经，内分泌，胃肠道，皮肤病conditions.ResultsWe确定了56例NSCLC和艾滋病谁收到PD-（L）1抑制剂。在治疗开始时，18%的患者有活动性AID症状，20%的患者正在接受免疫调节剂治疗AID。共有55%的患者发生了AID发作和/或免疫相关不良事件（irAE）。13名患者（占整个队列的23%）发生了AID加重，其中4名患者需要全身性皮质类固醇。21例患者（38%）发生免疫相关不良事件。在irAE中，74%为1级或2级，26%为3级或4级; 8例患者需要皮质类固醇治疗irAE。8例患者（14%）因irAE永久停用PD-（L）1治疗。免疫治疗的总有效率为22%。结论在接受PD-（L）1抑制剂治疗的非小细胞肺癌合并AID患者中，少数患者发生AID恶化。irAE的发生率与排除AID患者的临床试验中报告的发生率相似。不良事件通常是可管理的，很少导致永久性停止免疫治疗。
PurposeAlthough programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non-small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown.MethodsAs part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions.ResultsWe identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%.ConclusionIn patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.