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CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up
Fabian Müller (Otto-von-Guericke-Universität Magdeburg), Jule Taubmann (Otto-von-Guericke-Universität Magdeburg), Laura Bucci (Otto-von-Guericke-Universität Magdeburg), Artur Wilhelm (Otto-von-Guericke-Universität Magdeburg), Christina Bergmann (Otto-von-Guericke-Universität Magdeburg), Simon Völkl (Otto-von-Guericke-Universität Magdeburg), Michael Aigner (Otto-von-Guericke-Universität Magdeburg), Tobias Rothe (Otto-von-Guericke-Universität Magdeburg), Ioanna Minopoulou (Otto-von-Guericke-Universität Magdeburg), Carlo Tur (Università Cattolica del Sacro Cuore, Otto-von-Guericke-Universität Magdeburg), Johannes Knitza (Otto-von-Guericke-Universität Magdeburg), Soraya Kharboutli (Otto-von-Guericke-Universität Magdeburg), Sascha Kretschmann (Otto-von-Guericke-Universität Magdeburg), Ingrid Vášová (Otto-von-Guericke-Universität Magdeburg), Silvia Spoerl (Otto-von-Guericke-Universität Magdeburg), Hannah Reimann (Otto-von-Guericke-Universität Magdeburg), Luis Enrique Munoz (Otto-von-Guericke-Universität Magdeburg), Roman G. Gerlach (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Simon Schäfer (Otto-von-Guericke-Universität Magdeburg), Ricardo Grieshaber‐Bouyer (Otto-von-Guericke-Universität Magdeburg), Anne‐Sophie Korganow (Hôpital Civil, Strasbourg, Université de Strasbourg), Dominique Farge (Université Paris Cité, Hôpital Saint-Louis), Dimitrios Mougiakakos (Otto-von-Guericke-Universität Magdeburg), Aline Bözec (Otto-von-Guericke-Universität Magdeburg), Thomas Winkler (Otto-von-Guericke-Universität Magdeburg), Gerhard Krönke (Charité – Universitätsmedizin Berlin, Otto-von-Guericke-Universität Magdeburg), Andréas Mackensen (Otto-von-Guericke-Universität Magdeburg), Georg Andreas Schett (Università Cattolica del Sacro Cuore, Karolinska Institutet)
Résumé : 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.).