Journal Club : Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus
© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
ACR open rheumatology - 5(2023), 11 vom: 10. Nov., Seite 624-628 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Boulougoura, Afroditi [VerfasserIn] |
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Date Revised 15.11.2023 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1002/acr2.11614 |
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| 500 | |a Date Revised 15.11.2023 | ||
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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