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

Front Immunol. 2021 Feb 25:12:552429. doi: 10.3389/fimmu.2021.552429. eCollection 2021.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Cell Maturation Antigen / immunology
  • Biomarkers
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / secondary*
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Immunotherapy, Adoptive / methods
  • Male
  • Middle Aged
  • Multiple Myeloma / complications*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology*
  • Multiple Myeloma / therapy
  • Neurotoxicity Syndromes / diagnosis
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / therapy*
  • Receptors, Chimeric Antigen / immunology
  • Symptom Assessment
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • B-Cell Maturation Antigen
  • Biomarkers
  • Glucocorticoids
  • Receptors, Chimeric Antigen

Associated data

  • ClinicalTrials.gov/NCT03196414