Immu-45. reversible parkinsonism after bcma-directed car t cell administration

Abstract B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR)T cell therapy has revolutionized the treatment of patients with relapsed or refractory multiple myeloma (MM), resulting in FDA-approval of two products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). In addition to immune effector cell associated neurotoxicity syndrome (ICANS), a novel hypokinetic movement disorder resembling parkinsonism has been reported with BCMA-targeting CAR. Cases reported to date have been irreversible or fatal, and guidance on how to manage this complication is limited. Here we describe a patient with MM who developed features of parkinsonism on day 24 post ide-cel infusion which were apparently reversible with supportive care and dexamethasone. A 77 year-old man with MM received standard lymphodepletion followed by ide-cel. He developed grade 1 cytokine release syndrome (CRS) for which he received tociluzumab, followed by transient expressive aphasia (grade 2 ICANS) on day 23. Brain MRI showed no structural abnormality. On day 24 he developed new tremor and gait impairment. Neurologic examination revealed cogwheeling in bilateral wrists, hypomimia, soft speech, and slowed gait. Lumbar puncture and electroencephalogram were unremarkable. FDG-PET brain did not show basal ganglia hypometabolism or abnormal avidity. Lymphocyte percentage was elevated and correlated with a high level of circulating CAR+ T cells. He was started on dexamethasone 10 mg q day, receiving a total of 17 days of steroids with improvement in symptoms. At day 60, ambulation was improved and cogwheeling and hypomimia resolved. By day 90, all neurological symptoms had resolved. Improvement remained sustained as of last follow up day 120. To our knowledge, this is the first case report of steroid responsive parkinsonism after BCMA-CAR therapy. Our report supports close neurological monitoring of patients beyond 30 days after BCMA-CAR and suggests that intervening early in the setting of hypokinetic movement disorders may lead to sustained reversal of symptoms.