POS0876 EFFECT OF ANTI-CD19 CAR T CELL THERAPY IN THE BONE MARROW OF PATIENTS WITH SYSTEMIC AUTOIMMUNE DISEASES

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Background: Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has emerged as a promising treatment option for patients with systemic autoimmune diseases that are resistant to conventional therapies [1]. Its efficacy is believed to stem from their ability to eliminate B cells in tissues. Recent findings have demonstrated that anti-CD19 CAR T cell therapy effectively eliminates B cells within the lymph nodes of patients with systemic autoimmune diseases [2], however the impact on the bone marrow remains to be determined. Objectives: To investigate the effect of anti-CD19 CAR T cell therapy in the bone marrow of patients with systemic autoimmune diseases. Methods: Three patients with severe, treatment-resistant systemic autoimmune diseases (Table 1) received autologous anti-CD19 CAR T cell therapy following conditioning therapy with fludarabine and cyclophosphamide [3, 4]. Bone marrow biopsies were performed prior to therapy (Patients 2 and 3) and after therapy (Patient 1 and 2 at week 16, and Patient 3 at week 7). Immune phenotyping of B and T cells was conducted via flow cytometry. Results: Treatment with KYV-101 appeared to be safe (Table 1). Stable clinical improvement was achieved following anti-CD19 CAR T cell therapy, even after discontinuation of all other immunosuppressive treatments. Bone marrow biopsies were performed on two patients (Patients 1 and 3) prior to peripheral B cell reconstitution. In these patients, B cells, particularly CD19+ plasmablasts and CD19+ plasma cells, were significantly reduced at weeks 16 and 7, respectively (Figure 1). In contrast, the bone marrow biopsy in patient 2 was conducted after B cell reconstitution. At week 16, post-anti-CD19 CAR T cell therapy and following B cell reconstitution, B cells in the bone marrow of patient 2 predominantly exhibited a naive/transitional phenotype, suggesting the re-emergence of naive/transitional B cells (Figure 1). Additionally, memory B cells were decreased, and CD19+ plasmablasts and plasma cells were notably diminished (Figure 1). Conclusion: This study highlights that anti-CD19 CAR T cell therapy, combined with standard lymphodepleting regimens, promotes remission in patients with systemic autoimmune diseases by fully depleting B cells within primary lymphatic organs. REFERENCES: [1] Müller F et al. N Engl J Med 2024. [2] Tur C et al. Ann Rheum Dis 2024. [3] Minopoulou I et al. Ann Rheum Dis 2025. [4] Albach F et al. Rheumatology (Oxford) 2025. Figure 1Dot plots showing FACS analysis of B cells from the bone marrow before (Patient 2 and 3) and after (Patient 1, 2 and 3) anti-CD19 CAR T cell therapy stained with anti-CD38 and anti-CD27. Table 1Patient characteristics.CharacteristicPatient 1Patient 2Patient 3DiseaseSLEOverlap Syndrome of SSc with RAPR3+ AAVAge463252SexMaleFemaleMalePrevious immunosuppressivetreatmentsglucocorticoids,cyclophosphamide,belimumab,hydroxychloroquine,methotrexate,leflunomide,anifrolumab,mycophenolate mofetilglucocorticoids, methotrexate, azathioprine,hydroxychloroquine,tocilizumab,nintedanibglucocorticoids,cyclophosphamide, rituximab, azathioprine, mycophenolate mofetil, methotrexateSafety and tolerabilityCRS=Grade 1No ICANSCRS=Grade 2No ICANSCRS=Grade 1No ICANSDisease activity before anti-CD19 CAR T cell therapySLEDAI-2K=14mRSS=9FVC=54%DLCO=43%DAS28-CRP=2.02BVAS=2VDI=5Disease activity after anti-CD19 CAR T cell therapySLEDAI-2K=4(at month 11)mRSS=3FVC=55%DLCO=48%DAS28-CRP=1.4(at month 9)BVAS=0VDI=5(at month 7)BVAS, Birmingham vasculitis activity score; CAR, chimeric antigen receptor; CRS, cytokine release syndrome; DAS28-CRP, disease activity score for rheumatoid arthritis with CRP; DLCO, diffusing capacity of the lungs for carbon monoxide; FVC, forced vital capacity; ICANS, immune effector cell-associated neurotoxicity; mRSS, modified Rodnan skin score; PR3+ AAV, proteinase 3+ ANCA-associated vasculitis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SLEDAI-2K, systemic lupus erythematosus disease activity index 2000; SSc, systemic sclerosis; VDI, vasculitis damage index. Acknowledgements: NIL . Disclosure of Interests: Ioanna Minopoulou AbbVie, Novartis, Lilly, Artur Wilhelm: None declared, Fredrik N. Albach: None declared, Arnd Kleyer: None declared, Edgar Wiebe: None declared, Anja Fleischmann: None declared, Mareike Frick: None declared, Frederik Damm: None declared, Dominic Borie Kyverna Therapeutics, Vincent Casteleyn: None declared, Robert Biesen: None declared, Thomas Dörner AbelZeta, BMS, J&J, Novartis, Roche/Genentech, Tobias Alexander: None declared, Jan Zernicke: None declared, Lukas Hinkelmann: None declared, Elpida Phitak: None declared, Norman Michael Drzeniek: None declared, Kamran Movassaghi: None declared, Marie Luise Hütter-Krönke: None declared, Eva Schrezenmeier: None declared, Adrian Schreiber: None declared, Udo Schneider: None declared, Georg Schett: None declared, Lars Bullinger: None declared, Gerhard Krönke: None declared, Olaf Penack Alexion, Gilead, Jazz, MSD, Neovii, Novartis, Pfizer and Therakos, David Simon AbbVie, Alfasigma, Bristol-Myers Squibb, Janssen-Cilag, Lilly, Novartis, UCB. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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