Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Med. 2021 Dec;27(12):2099-2103. doi: 10.1038/s41591-021-01564-7. Epub 2021 Dec 10.
B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM). Here, we describe the case of a patient with MM who was enrolled in the CARTITUDE-1 trial ( NCT03548207 ) and who developed a progressive movement disorder with features of parkinsonism approximately 3 months after ciltacabtagene autoleucel BCMA-targeted CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration. We show BCMA expression on neurons and astrocytes in the patient's basal ganglia. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting that this might be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade 3 or higher parkinsonism on the phase 2 ciltacabtagene autoleucel trial and of grade 3 parkinsonism in the idecabtagene vicleucel package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies.
B 细胞成熟抗原 (BCMA) 是多发性骨髓瘤 (MM) 嵌合抗原受体 (CAR)-T 细胞治疗中的一个重要肿瘤相关靶点。在这里，我们描述了一名多发性骨髓瘤患者的病例，该患者参加了 CARTITUDE-1 试验（NCT03548207），在 ciltacabtagene autoleucel BCMA 靶向 CAR-T 细胞输注后约 3 个月出现进行性运动障碍，表现为帕金森病特征，伴有 CAR-T 细胞在血液和脑脊液中的持续存在，以及基底神经节淋巴细胞浸润。我们在患者基底神经节中显示神经元和星形胶质细胞上的 BCMA 表达。公共转录组数据集进一步证实了正常人大脑中尾状核的 BCMA RNA 表达，表明这可能是抗 BCMA 治疗的一个靶点效应。鉴于在 ciltacabtagene autoleucel 二期试验中有 3 名患者出现 3 级或更高级别的帕金森病，以及 idecabtagene vicleucel 说明书中有 3 级帕金森病的报道，我们的发现支持对接受 BCMA 靶向 T 细胞治疗的患者进行密切的神经学监测。
