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:Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.
Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.
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免疫效应细胞相关神经毒性综合征(ICANS)是嵌合抗原受体(CAR)T细胞治疗的已知副作用,免疫检查点抑制剂治疗后也偶有报道。双特异性单克隆抗体glofitamab相关ICANS则较少见。一名63岁男性患者,37岁时确诊套细胞淋巴瘤,50岁时诊断侵袭性大细胞B细胞淋巴瘤。尽管接受充分化疗、免疫治疗、自体干细胞移植及CAR-T 治疗,患者仍多次复发,包括61岁时脑膜癌病及62岁时脑内淋巴瘤。
因此开始使用glofitamab。第9个周期后1周,患者出现嗜睡、行为改变、找词困难、失语、局灶进展为双侧强直阵挛发作及局灶起始癫痫,使用左乙拉西坦、丙戊酸、劳拉西泮和咪达唑仑治疗16天后症状缓解。排除感染、电解质紊乱、代谢异常、心血管疾病和淋巴瘤复发后,怀疑为glofitamab相关ICANS,并给予anakinra。该病例显示,glofitamab可引起嗜睡、行为改变、失语和癫痫等ICANS表现;存在结构性脑异常者可能更易发生。
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been described with immune checkpoint inhibitors as well. Glofitamab-associated ICANS with a bispecific monoclonal antibody has rarely been reported. The patient is a 63-year-old male with a history of mantle cell lymphoma, diagnosed at age 37, and aggressive large-cell B-cell lymphoma, diagnosed at age 50. Despite adequate chemotherapy, immunotherapy, autologous stem cell transplantation, and CAR T-cell therapy, there were several relapses, including meningeal carcinomatosis at age 61 and intracerebral lymphoma at age 62.
For this reason, glofitamab was started. One week after the ninth cycle, the patient developed drowsiness, behavioral changes, word-finding difficulties, aphasia, focal to bilateral tonic-clonic seizures, and focal onset seizures, which resolved after 16 days with levetiracetam, valproic acid, lorazepam, and midazolam.
Since there was no infectious disease, electrolyte disturbance, metabolic disorder, cardiovascular disease, or relapse of lymphoma, glofitamab-associated ICANS was suspected, and anakinra was administered. The case shows that ICANS with drowsiness, behavioral changes, aphasia, and seizures can develop with glofitamab and that patients with structural brain abnormalities may be prone to this.
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