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:Reversible cerebral vasoconstriction syndrome following ciltacabtagene autoleucel therapy for relapsed multiple myeloma: a case report.
Reversible cerebral vasoconstriction syndrome following ciltacabtagene autoleucel therapy for relapsed multiple myeloma: a case report.
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西达基奥仑赛(cilta-cel)是一种靶向BCMA的CAR-T 疗法,已获批用于复发/难治性多发性骨髓瘤(RRMM)。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)较为常见,但可逆性脑血管收缩综合征(RCVS)是cilta-cel治疗后此前未曾报道的并发症。一名63岁女性RRMM患者(IgA lambda,t(14;16)),无血管危险因素,在接受包括自体移植在内的两种既往治疗后接受cilta-cel。CAR-T 输注后第+10天,她发生1级CRS,经tocilizumab和血管升压药(包括midodrine)治疗。第+19天,她出现头痛、腿部无力和精细运动技能丧失。
神经影像学显示多灶性脑动脉狭窄和缺血性卒中,最初提示血管炎。后续影像学确诊为RCVS(RCVS2评分9)。使用皮质类固醇、anakinra、siltuximab、环磷酰胺、verapamil和nimodipine治疗未能阻止神经功能恶化,导致右侧偏瘫以及Gerstmann综合征和Balint综合征。至第+69天,CT血管造影显示狭窄已消退,但神经功能缺损持续存在。本病例将RCVS确定为cilta-cel治疗后一种新型、危及生命的并发症,可能与CRS、tocilizumab或midodrine有关。这强调了对CAR-T 神经毒性进行更广泛鉴别诊断和个体化管理的必要性,值得进一步研究。
Ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T therapy, is approved for relapsed/refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common, but reversible cerebral vasoconstriction syndrome (RCVS) is a previously unreported complication following cilta-cel. A 63-year-old female with RRMM (IgA lambda, t(14;16)), no vascular risk factors, received cilta-cel after two prior therapies, including autologous transplantation. On day +10 post-CAR-T infusion, she developed grade 1 CRS, managed with tocilizumab and vasopressors, including midodrine. On day +19, she presented with headache, leg weakness, and loss of fine motor skills.
Neuroimaging showed multifocal cerebral stenosis and ischemic strokes, initially suggesting vasculitis. Subsequent imaging confirmed RCVS (RCVS2 score 9). Treatment with corticosteroids, anakinra, siltuximab, cyclophosphamide, verapamil, and nimodipine failed to halt neurological decline, resulting in right-sided hemiplegia and Gerstmann's and Balint's syndromes.
By day +69, CT angiography showed resolved stenosis, but neurological deficits persisted. This case identifies RCVS as a novel, life-threatening complication following cilta-cel, possibly linked to CRS, tocilizumab, or midodrine. It underscores the need for broader differential diagnoses and tailored management for CAR-T neurotoxicities, warranting further research.
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