CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year

Neurol Neuroimmunol Neuroinflamm. 2024 Sep;11(5):e200292. doi: 10.1212/NXI.0000000000200292. Epub 2024 Aug 6.

Abstract

Objectives: In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells.

Methods: CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis and infused after a conventional lymphodepleting regimen.

Results: A 18-year-old man developed 2 episodes of myelitis associated with serum MOG-IgG, which were followed by 6 episodes of left optic neuritis (ON) and sustained the presence of MOG-IgG over 6 years despite multiple immunotherapies. After the sixth episode of ON, accompanied by severe residual visual deficits, CAR T-cell treatment was provided without complications. Follow-up of cell counts showed complete depletion of CD19+ B cells at day +7; reconstituted B cells at day +141 showing a naïve B-cell phenotype, and low or absent memory B cells and plasmablasts for 1 year. MOG-IgG titers have remained undetectable since CAR T-cell infusion. The patient had an early episode of left ON at day +29, when MOG-IgG was already negative, and since then he has remained free of relapses without immunotherapy for 1 year.

Discussion: This clinical case shows that CD19-directed CAR T-cell therapy is well-tolerated and is a potential treatment for patients with refractory MOGAD.

Classification of evidence: This provides Class IV evidence. It is a single observational study without controls.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antigens, CD19* / immunology
  • Follow-Up Studies
  • Humans
  • Immunotherapy, Adoptive*
  • Male
  • Myelin-Oligodendrocyte Glycoprotein* / immunology
  • Optic Neuritis / immunology
  • Optic Neuritis / therapy
  • Receptors, Chimeric Antigen / immunology
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD19
  • Myelin-Oligodendrocyte Glycoprotein
  • CD19 molecule, human
  • MOG protein, human
  • Receptors, Chimeric Antigen