Neurocognitive and Movement Disorder After BCMA-Targeting CAR-T Cell Therapy

Van Oekelen O, Aleman A, Upadhyaya B, et al. Neurocognitive and Hypokinetic Movement Disorder with Features of Parkinsonism After BCMA-Targeting CAR-T Cell Therapy. Nature Medicine. 2021; 27: 2099 (doi: 10.1038/s41591-021-01564-7).

New research highlights the need for close neurological monitoring of patients receiving B-cell maturation antigen (BCMA)-targeted T cell therapies, following reports of three patients with grade 3 or higher parkinsonism in the Phase II ciltacabtagene autoleucel trial and of grade 3 parkinsonism in the idecabtagene vicleucel package insert. In this report, researchers present the case of a patient with multiple myeloma (MM) who was participating in the CARTITUDE-1 trial and developed a progressive movement disorder with features of parkinsonism about 3 months after infusion with ciltacabtagene autoleucel BCMA-targeted chimeric antigen receptor (CAR)-T cells. The condition was associated with CAR-T cell persistence in the blood and cerebrospinal fluid and basal ganglia lymphocytic infiltration. BCMA expression was observed in the basal ganglia on neurons and astrocytes. Using public transcriptomic datasets, BCMA RNA expression was confirmed in the caudate of normal human brains, "suggesting that this might be an on-target effect of anti-BCMA therapy," the researchers write.

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Tags: BCMA, Targeting, CAR T, Research, CAR T-Cell Therapy, CAR T-cell, neurocognitive, movement, disorder, NMD