POS0819 ANTI-CD19 CAR T CELL THERAPY IN SYSTEMIC SCLEROSIS – EXPERIENCES FROM TUEBINGEN IN 3 PATIENTS
Authors: J. Henes, A. C. Pecher, L. Hensen, R. Klein, A. Stanger, C. Faul, W. Bethge, C. Lengerke
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Chimeric antigen receptor (CAR) T cell therapy directed against cluster of differentiation (CD) 19 is a new promising therapeutic approach in autoimmune diseases. <h3>Objectives:</h3> To evaluate feasibility and safety of CD19 directed CAR T cell therapy in three patients with systemic sclerosis (SSc) not qualifying for autologous stem cell transplantation (HSCT) <h3>Methods:</h3> We offered a rescue therapy with CD19 CAR T cells produced at our good manufacturing practice (GMP) facility at the university Hospital Tuebingen to three patients with severe, life-threatening SSc. Patients stopped their immunosuppression for leukapheresis 14 days in advance and all were treated with a conditioning regimen with fludarabine (25 mg/m<sup>2</sup> [day -5 until day -3 day) and cyclophosphamide (CYC) (1000 mg/m<sup>2</sup>; day -3 before) followed by infusion of CAR T cells (manufactured by transduction of autologous T cells with a CD19 lentiviral vector kindly provided by Miltenyi Biotec, Germany, and amplification in the CliniMACS Prodigy system) <h3>Results:</h3> The first patient is a 51-year-old female with limited cutaneous (lc) SSc and severe interstitial lung disease and cardiac manifestation. In addition, she suffered from severe gastrointestinal involvement with &gt;20kg loss of body weight, reflux and gastric bleeding. Despite pre-treatment with CYC, mycophenolate mofetil (MMF) and nintedanib (NIN) she still showed signs of progressive disease with severe gastral paresis when she first presented at our hospital. She was treated with anti-CD19 CAR T cells in July 2023. Since then she could gain weight (5kg) for the first time and skin and lung-function improved (Figure 1). The second patient is a 42-year old female with lcSSc with severe lung manifestation and pre-treatment with methotrexate, MMF, ciclosporine A (CSA), hydroxychloroquine, CYC, NIN and rituximab (RTX). At first presentation at our center, lung-function was already too impaired to qualify for autologous stem cell transplantation. We treated her with CAR T cells in November 2023. No side effects were present. The third (male) patient with dcSSc was treated with HSCT in February 2022 with good response (mRSS dropped from 31 to 17). However, he experienced a severe relapse after COVID 19 infection in October 2022 and we initiated MTX and tocilizumab (TCZ) which only led to a moderate stabilization of disease activity. In July 2023 he experienced new ventricular flatter as sign of ongoing cardiac disease activity and we decided for CAR T cell therapy, which occurred in December 2023. In all 3 patients only mildest side effects with Cytokine release syndrome grade 1 and no Immune effector cell-associated neurotoxicity syndrome (ICANS) or infectious complication were observed. <h3>Conclusion:</h3> Anti-CD 19 directed CAR T cell therapy was feasible and safe in these 3 SSc patients that had contraindications for HSCT or even relapsed after HSCT. Patient 1 shows promising efficacy after a 4-month follow-up. Follow-up safety/efficacy data in all 3 patients will be presented at the meeting. <h3>REFERENCES: NIL. Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Jörg Henes Miltenyi, Ann-Christin Pecher: None declared, Luca Hensen: None declared, Reinhild Klein: None declared, Anna Stanger: None declared, Christoph Faul: None declared, Wolfgang Bethge: None declared, Claudia Lengerke: None declared.