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一名接受辅助性帕博利珠单抗治疗的黑色素瘤患者出现细胞因子释放综合征和免疫效应细胞相关神经毒性综合征

Cytokine release syndrome and immune effector cell‑associated neurotoxicity syndrome in a melanoma patient treated with adjuvant pembrolizumab.

作者信息

Ochenduszko Sebastian, Landete Lamberto, Martinez David Collado, Feria Ana García, Francés Carla, Torregrosa María Dolores, Maiques Inmaculada Maestu

机构信息

Department of Oncology, Doctor Peset University Hospital, 46017 Valencia, Spain.

Department of Neurology, Doctor Peset University Hospital, 46017 Valencia, Spain.

出版信息

Exp Ther Med. 2024 Sep 11;28(5):423. doi: 10.3892/etm.2024.12712. eCollection 2024 Nov.

Abstract

The emergence of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with solid tumors. However, along with their efficacy, new toxicities related to immune system activation have surfaced, some of which pose life-threatening risks. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are among the serious, albeit rare, immune-related adverse effects (irAEs) observed. Although commonly associated with hematologic malignancies and chimeric antigen receptor T cell therapies, CRS has been reported in patients treated with ICIs, with ICANS being a less documented complication. The present study presents a case report of a 76-year-old patient with resected melanoma who developed clinical symptoms of CRS and ICANS following adjuvant pembrolizumab therapy. The patient presented with neurological symptoms of weakness and encephalopathy with confusion, bradypsychia, dysarthria, tremors and visual hallucinations. Laboratory tests revealed elevated serum levels of tumor necrosis factor-alpha and interleukin-6 along with inflammatory markers, hepatic and renal dysfunction, as well as rapidly progressive normochromic-normocytic anemia. Treatment with corticosteroids led to rapid symptom resolution, albeit with subsequent symptom recurrence after tapering its dose. This case underscores the importance of recognizing and managing irAEs associated with ICIs and highlights the need for vigilant monitoring and individualized therapeutic approaches.

摘要

免疫检查点抑制剂(ICI)的出现显著改善了实体瘤患者的预后。然而,随着其疗效的显现,与免疫系统激活相关的新毒性也浮出水面,其中一些毒性带来了危及生命的风险。细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)是观察到的严重(尽管罕见)的免疫相关不良反应(irAE)。虽然CRS通常与血液系统恶性肿瘤和嵌合抗原受体T细胞疗法相关,但在接受ICI治疗的患者中也有报道,而ICANS作为一种并发症记录较少。本研究报告了一例76岁的黑色素瘤切除患者,在辅助使用帕博利珠单抗治疗后出现了CRS和ICANS的临床症状。患者出现了虚弱和脑病的神经症状,伴有意识模糊、精神迟缓、构音障碍、震颤和视幻觉。实验室检查显示血清肿瘤坏死因子-α和白细胞介素-6水平升高,同时伴有炎症标志物、肝肾功能障碍以及快速进展的正色素正细胞性贫血。使用皮质类固醇治疗后症状迅速缓解,尽管在剂量逐渐减少后症状随后复发。该病例强调了识别和管理与ICI相关的irAE的重要性,并突出了警惕监测和个体化治疗方法的必要性。

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