@article{7cda9a01801845cfad9883c6700ebbe3,
title = "Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy",
abstract = "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{\textquoteright}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.",
author = "{Van Oekelen}, Oliver and Adolfo Aleman and Bhaskar Upadhyaya and Sandra Schnakenberg and Deepu Madduri and Somali Gavane and Julie Teruya-Feldstein and Crary, {John F.} and Fowkes, {Mary E.} and Stacy, {Charles B.} and Seunghee Kim-Schulze and Adeeb Rahman and Alessandro Lagan{\`a} and Brody, {Joshua D.} and Miriam Merad and Sundar Jagannath and Samir Parekh",
note = "Funding Information: O.V.O. has no relevant conflicts to disclose. A.A. has no relevant conflicts to disclose. B.U. has no relevant conflicts to disclose. S.S. has no relevant conflicts to disclose. S.S. is currently employed by Sema4 but was not working for the company at the time of preparation of the manuscript. D.M. has worked as a consultant for Bristol Myers Squibb, Celgene, Foundation Medicine, GSK, Janssen, Kinevant and Sanofi and has received grant and research support from Allogene, Amgen, Bristol Myers Squibb, Celgene, Janssen and Regeneron. D.M. is currently employed by Johnson & Johnson but was not working for the company at the time of preparation of the manuscript. S.G. has no relevant conflicts to disclose. J.T.F. has no relevant conflicts to disclose. J.F.C. has no relevant conflicts to disclose. C.B.S. is a member of the ciltacabtagene autoleucel Risk Evaluation and Mitigation Strategy advisory board. S.K.S. has no relevant conflicts to disclose. A.R. is currently employed by Immunai but was not working for the company at the time of preparation of the manuscript. A.L. has no relevant conflicts to disclose. J.D.B. has received consulting fees from Celldex, Genentech, Gilead, Janssen, Kite and Merck and has received research funding or reagents provided by Celldex, Genentech, Janssen, Kite and Merck. M.M. has no relevant conflicts to disclose. S.J. has received consulting fees from Bristol Myers Squibb, Janssen, Karyopharm, Merck, Sanofi and Takeda. S.P. receives research funding from Amgen, Celgene/Bristol Myers Squibb and Karyopharm and consulting fees from Foundation Medicine. All other authors declare no competing interests. Funding Information: The authors would like to thank T. Dawson, H. Xie, M. Patel and the rest of the staff members at the Human Immune Monitoring Center at the Icahn School of Medicine for sample management and their help conducting omics assays. Furthermore, we would like to thank M. Garcia-Barros and R. Brody from the Biorepository and Pathology Core at the Icahn School of Medicine for immunohistochemistry staining. S.P. acknowledges support by the National Cancer Institute (NCI) (R01 CA244899 and R01 CA252222) and receives research funding from Amgen, Celgene/Bristol Myers Squibb and Karyopharm. M.M. acknowledges support from the National Institute of Allergy and Infectious Diseases (U24 AI118644-05S1, U19 AI128949 and U19 AI118610), from the NCI (R01 CA254104, R01 CA257195 and P30 CA196521-05S2), from a Fast Grant (George Mason University), from the Gates Foundation and from the Samuel Waxman Cancer Research Foundation. J.B. acknowledges support from the NCI (R01 CA246239-01). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = dec,
doi = "10.1038/s41591-021-01564-7",
language = "English",
volume = "27",
pages = "2099--2103",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "12",
}