CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.

Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spörl S, Reimann H, Munoz LE, Gerlach R, Schäfer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Krönke G, Mackensen A, Schett G (2024)

Publication Type: Journal article

Publication year: 2024

Journal

New England Journal of Medicine Massachusetts Medical Society

Book Volume: 390

Pages Range: 687-700

Journal Issue: 8

DOI: 10.1056/NEJMoa2308917

Abstract

BACKGROUND: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission. METHODS: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded. RESULTS: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization. CONCLUSIONS: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.).

Authors with CRIS profile

Fabian Müller Department of Medicine 5 – Haematology and Oncology Jule Taubmann Department of Medicine 3 – Rheumatology and Immunology Laura Bucci Department of Medicine 3 – Rheumatology and Immunology Artur Wilhelm Department of Medicine 3 – Rheumatology and Immunology Christina Bergmann Department of Medicine 3 – Rheumatology and Immunology Simon Völkl Department of Medicine 5 – Haematology and Oncology Tobias Rothe Department of Medicine 3 – Rheumatology and Immunology Ioanna Minopoulou Department of Medicine 3 – Rheumatology and Immunology Johannes Knitza Department of Medicine 3 – Rheumatology and Immunology Ingrid Vasova Lehrstuhl für Innere Medizin V Silvia Spörl Department of Medicine 5 – Haematology and Oncology Hannah Reimann Department of Medicine 5 – Haematology and Oncology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Roman Gerlach Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Aline Bozec Thomas Winkler Professur für Genetik Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology Andreas Mackensen Lehrstuhl für Innere Medizin V Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Université Sorbonne Paris Cité FR France (FR) Université de Strasbourg (UDS) FR France (FR)

How to cite

APA:

Müller, F., Taubmann, J., Bucci, L., Wilhelm, A., Bergmann, C., Völkl, S.,... Schett, G. (2024). CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. New England Journal of Medicine, 390(8), 687-700. https://doi.org/10.1056/NEJMoa2308917

MLA:

Müller, Fabian, et al. "CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up." New England Journal of Medicine 390.8 (2024): 687-700.

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