• N. Engl. J. Med. · Feb 2024

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

    • Fabian Müller, Jule Taubmann, Laura Bucci, Artur Wilhelm, Christina Bergmann, Simon Völkl, Michael Aigner, Tobias Rothe, Ioanna Minopoulou, Carlo Tur, Johannes Knitza, Soraya Kharboutli, Sascha Kretschmann, Ingrid Vasova, Silvia Spoerl, Hannah Reimann, Luis Munoz, Roman G Gerlach, Simon Schäfer, Ricardo Grieshaber-Bouyer, Anne-Sophie Korganow, Dominique Farge-Bancel, Dimitrios Mougiakakos, Aline Bozec, Thomas Winkler, Gerhard Krönke, Andreas Mackensen, and Georg Schett.
    • From the Departments of Internal Medicine 5-Hematology and Oncology (F.M., S.V., M.A., S. Kharboutli, S. Kretschmann, I.V., S. Spoerl, H.R., A.M.) and Internal Medicine 3-Rheumatology and Immunology (J.T., L.B., A.W., C.B., T.R., I.M., C.T., J.K., L.M., R.G.-B., A.B., G.K., G.S.), Deutsches Zentrum Immuntherapie (F.M., J.T., L.B., A.W., C.B., S.V., M.A., T.R., I.M., C.T., J.K., S. Kharboutli, S. Kretschmann, I.V., S. Spoerl, H.R., L.M., R.G.-B., A.B., G.K., A.M., G.S.), and the Institute of Clinical Microbiology, Immunology, and Hygiene (R.G.G.), Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, and the Department of Biology, Division of Genetics, Nikolaus-Fiebiger Center for Molecular Medicine, FAU Erlangen-Nürnberg (S. Schäfer, T.W.), Erlangen, the Department of Hematology and Oncology and Health Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University, Magdeburg (D.M.), and the Department of Rheumatology, Charité-Universitätsmedizin Berlin, Berlin (G.K.) - all in Germany; the Department of Rheumatology, Catholic University of the Sacred Heart, Rome (C.T., G.S.); the Department of Clinical Immunology, Nouvel Hôpital Civil, Strasbourg University, Strasbourg (A.-S.K.), and Centre de Référence des Maladies Auto-immunes Systémiques Rares d'Ile-de-France, Hôpital Saint-Louis and Université Paris Cité, Paris (D.F.-B.) - both in France; and Karolinska Institutet, Stockholm (G.S.).
    • N. Engl. J. Med. 2024 Feb 22; 390 (8): 687700687-700.

    BackgroundTreatment 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.MethodsWe 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.ResultsThe 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.ConclusionsIn 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.).Copyright © 2024 Massachusetts Medical Society.

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