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

B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM). We describe the case of a MM patient, enrolled in the CARTITUDE-1 trial (NCT03548207), who developed a progressive movement disorder with features of parkinsonism approximately three months after BCMA-targeted ciltacabtagene autoleucel CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration. We demonstrate BCMA expression on neurons and astrocytes in the basal ganglia of the patient. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting this may be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade ≥3 parkinsonism on the phase 2 cilta-cel trial and of grade 3 parkinsonism in the idecabtagene vicleucel (ide-cel) package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies. We conducted CITE-seq on peripheral blood mononuclear cells (PBMC) of 1 healthy donor and 4 patients of the CARTITUDE-1 clinical trial. Samples of trial patients were collected at variable time after CAR-T infusion (range 14-128 days). Samples were split into two aliquots and were either "stimulated" or "unstimulated". Stimulated aliquots were incubated for 3hrs at 37ºC with PMA/Ionomycin. After these incubations the 10 aliquots were hashed and pooled. Sequencing was done using Illumina NextSeq (hashtag-oligos/HTO and antibody-derived tags/ADT) over four lanes (technical replicates) and using Illumina NovaSeq S2 (gene expression/GEX) over two lanes (technical replicates).