Targeting autoimmunity with CD19-CAR T-cell therapy: efficacy and seroconversion in diffuse systemic sclerosis and rheumatoid arthritis
Fredrik N. Albach, Ioanna Minopoulou, Artur Wilhelm, Robert Biesen, Arnd Kleyer, Edgar Wiebe, Anja Fleischmann, Mareike Frick, Frédérik Damm, Julia Gogolok, Sebastian Serve, Benjamin N. Locher, Dominic Borie, Vincent Casteleyn, Elise Siegert, Thomas E. Dorner, Tobias Alexander, Christian Furth, Jan Zernicke, Kamran Movassaghi, Marie Luise Hütter‐Krönke, Eva Schrezenmeier, Udo Schneider, Lars Bullinger, Gerhard Krönke, Olaf Penack, David Simón
Abstract
Dear Editor, Rapidly progressive diffuse SSc is a rare autoimmune connective-tissue disease characterized by heterogeneous clinical manifestations, making disease management challenging. Current therapeutic concepts are primarily aimed at suppressing inflammation and slowing down fibrotic remodelling, necessitating continuous, lifelong immunomodulatory therapy [1]. SSc can rarely coincide with RA, further complicating treatment [2]. B cells are considered key drivers of inflammation in both diseases. B-cell depletion with rituximab has shown efficacy in both SSc and RA but often fails to induce long-lasting remission [3, 4]. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has recently expanded the therapeutic armamentarium for autoimmune diseases, showing promising results in various SSc cases [5] and good tolerability in 30 patients with autoimmune diseases and a median follow-up of 12 months [6]. Additionally, one case report demonstrated the successful use of anti-CD19 CAR T-cell therapy in treating a patient with myasthenia gravis with coexisting RA [7]. Herein, we present the case of a 32-year-old female patient with a 6-year history of Scl-70-positive SSc and ACPA-positive RA. The patient presented with skin fibrosis, Raynaud’s phenomenon, recurrent digital ulcers, reduced oesophageal motility with reflux, pulmonary fibrosis and polyarthritis. Previous immunosuppressive treatments included glucocorticoids, methotrexate, azathioprine, hydroxychloroquine and tocilizumab. Furthermore, she was treated with nintedanib, sildenafil, nifedipine and repeated iloprost infusions. Despite these therapies, her course of SSc continuously progressed, although RA disease activity remained well-controlled (DAS28-CRP 2.02, CDAI 4). After discussing the risks and benefits of potential treatment options, the patient consented to undergo autologous anti-CD19 CAR-T-cell therapy in a shared decision.