ACR Open Rheumatology (Nov 2023)

Journal Club: Anti‐CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus

  • Afroditi Boulougoura,
  • Hannah Gendelman,
  • Natalya Surmachevska,
  • Vasileios C. Kyttaris

DOI
https://doi.org/10.1002/acr2.11614
Journal volume & issue
Vol. 5, no. 11
pp. 624 – 628

Abstract

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Objective Despite substantial advances in the treatment of systemic lupus erythematosus (SLE), some patients do not respond to the current state‐of‐the art therapies. This study assessed the tolerability and efficacy of CD19 chimeric antigen receptor (CAR) T cells in a small series of seriously ill and treatment‐resistant patients with SLE. Methods Five patients with SLE (four female patients and one male patient) with a median age of 22 (range 18–24) years, a median disease duration of 4 (range 1–9) years, and active disease (median Systemic Lupus Erythematosus Disease Activity Index score of 16 [range 8–16]) refractory to several immunosuppressive drug treatments were enrolled in a compassionate‐use CAR‐T cell program. Autologous T cells from patients with SLE were transduced with a lentiviral anti‐CD19 CAR vector, expanded, and reinfused at a dose of 1 × 106 CAR T cells per kilogram of body weight into the patients after lymphodepletion with fludarabine and cyclophosphamide. Results CAR T cells expanded in vivo and led to deep depletion of B cells, improvement of clinical symptoms, and normalization of laboratory parameters, including seroconversion of anti–double‐stranded DNA antibodies. Remission of SLE according to definition of remission in SLE criteria was achieved in all five patients after 3 months, and the median Systemic Lupus Erythematosus Disease Activity Index score after 3 months was 0 (range 2). Drug‐free remission was maintained during longer follow‐up (median of 8 [range 12] months after CAR‐T cell administration) and even after the reappearance of B cells, which was observed after a mean (±SD) of 110 ± 32 days after CAR‐T cell treatment. Reappearing B cells were naive and showed non–class‐switched B cell receptors. CAR‐T cell treatment was well tolerated, with only mild cytokine release syndrome. Conclusion These data suggest that CD19 CAR‐T cell therapy was feasible, tolerable, and effective in this small case series of refractory SLE. Nevertheless, larger placebo‐controlled trials are warranted.