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Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy

Authors :
Van Oekelen, Oliver
Aleman, Adolfo
Upadhyaya, Bhaskar
Schnakenberg, Sandra
Madduri, Deepu
Gavane, Somali
Teruya-Feldstein, Julie
Source :
Nature Medicine. December, 2021, Vol. 27 Issue 12, p2099, 5 p.
Publication Year :
2021

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'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. A progressive movement disorder in a patient with multiple myeloma treated with anti-BCMA CAR-T cells that might have been related to on-target activity in the brain supports prospective neurologic monitoring after BCMA-targeting therapies.<br />Author(s): Oliver Van Oekelen [sup.1] [sup.2] , Adolfo Aleman [sup.1] [sup.2] , Bhaskar Upadhyaya [sup.2] [sup.3] [sup.4] , Sandra Schnakenberg [sup.5] [sup.6] , Deepu Madduri [sup.2] [sup.3] , Somali Gavane [...]

Details

Language :
English
ISSN :
10788956
Volume :
27
Issue :
12
Database :
Gale General OneFile
Journal :
Nature Medicine
Publication Type :
Academic Journal
Accession number :
edsgcl.686972012
Full Text :
https://doi.org/10.1038/s41591-021-01564-7