CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cytokine release syndrome and immune effector cell‑associated neurotoxicity syndrome in a melanoma patient treated with adjuvant pembrolizumab.
Cytokine release syndrome and immune effector cell‑associated neurotoxicity syndrome in a melanoma patient treated with adjuvant pembrolizumab.
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免疫检查点抑制剂(ICIs)的出现显著改善了实体瘤患者的预后。然而,伴随其疗效而来的是与免疫系统激活相关的新毒性反应,其中一些具有危及生命的风险。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)是已观察到的严重但罕见的免疫相关不良事件(irAEs)。尽管CRS通常与血液系统恶性肿瘤和CAR-T 细胞治疗相关,但已有报道在接受ICIs治疗的患者中出现CRS,而ICANS则是较少被记录的并发症。
本研究报道了一例76岁黑色素瘤切除术后患者,在接受辅助帕博利珠单抗治疗后出现了CRS和ICANS的临床症状。患者表现为神经系统症状,包括乏力和脑病,伴有意识模糊、思维迟缓、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升高、肝肾功能障碍,以及快速进展的正色素正细胞性贫血。皮质类固醇治疗使症状迅速缓解,但在减量后症状复发。本病例强调了识别和管理与ICIs相关的irAEs的重要性,并突出了警惕性监测和个体化治疗方法的必要性。
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.
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