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) 是嵌合抗原受体 (CAR)-T 细胞治疗多发性骨髓瘤 (MM) 的重要肿瘤相关靶点。在这里，我们描述了一名 MM 患者的病例，该患者参加了 CARTITUDE-1 试验 (NCT03548207)，在 ciltacabtagene autoleucel BCMA 靶向 CAR-T 细胞输注后大约 3 个月出现了具有帕金森综合征特征的进行性运动障碍，相关CAR-T细胞在血液和脑脊液中持续存在，基底节淋巴细胞浸润。我们展示了患者基底节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脑尾状核中的 BCMA RNA 表达，表明这可能是抗 BCMA 治疗的靶向作用。