Case Report: Reversible Neurotoxicity and a Clinical Response Induced by BCMA-Directed Chimeric Antigen Receptor T Cells Against Multiple Myeloma With Central Nervous System Involvement

Abstract

Isolated central nervous system involvement in multiple myeloma (CNS-MM) is rare and carries extremely poor prognosis. Chimeric antigen receptor T cell therapy (CART) targeting B-cell maturation antigen (BCMA) is demonstrated as a promising strategy in MM treatment, but the clinical safety and efficacy of BCMA-CART against isolated CNS-MM remain elusive. Here we report on a 56-year-old male with refractory isolated CNS-MM who received autologous BCMA-CART therapy and developed grade 4 neurological complications. Cerebrospinal fluid (CSF) analyses showed significant expansion of CART cells and a substantially elevated interleukin-6 (IL-6) level. Intravenous methylprednisolone was administered and the symptoms resolved gradually. Unexpectedly, the level of IL-6 in the CSF was maintained for another 3 days even after the relief of the neurological symptoms. A partial response was achieved and sustained for 5.5 months. This is the first report describing a patient with isolated CNS-MM treated using BCMA-CART therapy. The results demonstrated that BCMA-CART cells administered intravenously trafficked into the CSF, eradicated tumor cells, and induced severe but reversible neurological adverse events. This single-patient report suggests that BCMA-CART therapy can be considered as an alternative option for isolated CNS-MM.

Clinical trial registration: ClinicalTrials.gov, identifier NCT03196414.

Keywords: case report; central nervous system involvement; chimeric antigen receptor T cell therpay; multiple myeloma; neurotoxicity.

Conflict of interest statement

CZ is an employee of Livzon Mabpharm, Inc and UniCar Therapy Ltd. XL and XS are employees of UniCar Therapy Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Zhang, Zhang, Zhou, Zhang, Chen, Chen, Wang, Sun, Lou, Qi, Kang, Yu, Wu and Li.

Figures

Figure 1

Brain imaging of the patient before and after CART treatment. (A) Brain MRI immediately before CART infusion. (B) The same region on day 30 after CART infusion. Red arrows indicate the location of one of the intracranial abnormalities. The patient was discharged on day 24, and panel (B) was done using a different MRI instrument in a local hospital in the patient’s hometown.

Figure 2

CART cells, IL-6 and important events of the patient before and after CART treatment. The level of IL-6 in the peripheral blood (serum, dot) and cerebrospinal fluid (CSF, nabla) and the number of CART cells in the peripheral blood (serum, triangle) and cerebrospinal fluid (CSF, diamond) were curved over time. Shadow boxes show the period when neurotoxic events were observed. NE, neurotoxic event; MP, methylprednisolone; DEX, dexamethasone.