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

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.

Figure 1. Clinical Course and Treatments From a Patient With Refractory MOGAD Treated With CD19-Directed CAR T-Cells

(A) Clinical course since the onset of the disease until 1 year after anti-CD19 CAR T-cell therapy, including the episodes of myelitis and optic neuritis. Treatments during the 6.9 years preceding CAR T-cell therapy included rituximab, IV immunoglobulins (IVIg), prednisone (PD), and mycophenolate mofetil. Due to the relapse on day +29, the patient received IV methylprednisolone (IVMP: 1 gr/day x 3) and plasma exchange (PE). Since disease onset, serum MOG-IgG was tested 13 times by live cell-based assay and all the tests showed seropositivity (median titer 1:160; range, 80–160); they became negative (<1:80) for the first time at day +29. The blue line shows the CD19⁺ B-cell count, and the orange line represents CAR copy number by PCR. (B) Optical coherence tomography obtained 7 days before CAR T-cell infusion shows substantial reduction in peripapillary retinal nerve fiber layer (RNFL) thickness in the left eye compared with the right eye (normal range), associated with (C) severe atrophy of the left optic nerve through its entire length (arrow) demonstrated by T2-FLAIR orbital MRI.

Figure 2. Assessment of B-Cell Population Before and After CD19-Directed CAR T-Cell Infusion (Day 0)

Panels indicate changes in the number or proportion of CD19⁺ B cells, naïve B cells, marginal zone B cells, memory B cells, transitional B cells, plasmablasts, and IgG concentration. The gray area indicates the normal range.

Figure 3. Cytokine Profile Before and 35 Days After CD19-Directed CAR T-Cell Infusion (Day 0)

Panels indicate the levels of proinflammatory (IL-6, TNF-alpha, IFN-gamma, IL-8, IL-17a, IL-18) and anti-inflammatory (IL-10) cytokines.