双刃剑-多器官功能障碍是双检查点免疫治疗的罕见并发症

Boykow Matthew, Patel Ami K, Sondhi Neil, M. Asif, I. Devarajan, Wercberger Eli
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摘要

对抗肿瘤。这种免疫检查点分子功能的破坏可导致免疫耐受的不平衡,从而导致不受控制的免疫反应。这可能在临床上表现为自身免疫样/炎症性副作用,对正常器官系统和组织造成附带损害。这些不良事件被称为“免疫相关不良事件”(irAEs),也被认为主要是由t细胞介导的,然而其他免疫细胞也可能在irAEs的发生中发挥作用,包括分泌介导毒性的抗体的B细胞,以及分泌炎症介质和细胞因子的粒细胞[1]。值得注意的是,由ICIs引起的心脏毒性的发生率很少见(发生在< 1%的患者中),但可能是暴发性的,可能致命。神经系统并发症也很罕见,当所有神经系统irae合并时,一项对59项临床试验的综述报道,CTLA-4抑制剂的发病率为3.8%,PD-1抑制剂为6%,联合治疗为12%,并且据报道,服用ICIs的患者中有0.3%患有脑炎。最后,在一项对3,695例接受ICIs治疗的随机对照试验的系统综述中,急性肾损伤的总发生率为2.2%(3级和4级肾事件发生率为0.6%)[4]。在这里,我们提出了一个独特的病例,突出了Opdivo和Yervoy诱导的irAEs对我们患者的影响,并探讨了这些单克隆抗体通过免疫检查点抑制剂诱导的脑炎引起中枢神经系统同时损伤的独特病例,通过急性失代偿性左心室心力衰竭引起心血管系统
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Double-Edged Sword - Multiorgan Dysfunction as a Rare Complication of Dual Checkpoint Immunotherapy
against the tumor. This disruption in the functioning of immune checkpoint molecules can lead to imbalances in immunologic tolerance that results in an unchecked immune response. This may clinically manifest with autoimmune-like/inflammatory side-effects, which cause collateral damage to normal organ systems and tissues. Such adverse events, termed ‘immunerelated adverse events’ (irAEs), are also thought to be principally T-cell mediated, however other immune cells may play a role in the development of irAEs, including B cells that secrete antibodies which mediate toxicity, as well as granulocytes that secrete inflammatory mediators and cytokines [1]. Of note, the incidence of cardiac toxicity owing to ICIs is rare (occur-ring in < 1% of patients) but can be fulminant and potentially fatal. Neurologic complications are also rare and when all neurological irAEs are pooled, an incidence of 3.8% for CTLA-4 inhibitors, 6% for PD-1 inhibitors and 12% for combination therapy has been reported in one review of 59 clinical trials, and encephalitis has been reported in 0.3% of patients taking ICIs. Lastly, an overall incidence of 2.2% was reported for acute kidney injury (0.6% for grades 3 and 4 renal events) in one systematic review of randomized controlled trials including 3,695 patients treated with ICIs [4]. Here we present a unique case that highlights the impact Opdivo and Yervoy induced irAEs had on our patient and explore this unique case of these monoclonal antibodies causing simultaneous damage to the central nervous system via immune checkpoint inhibitor induced encephalitis, cardiovascular system via acute decompensated left ventricular heart failure Introduction
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