Anti-CD19 Chimeric Antigen Receptor T Cell Therapy Induces Multicompartmental B Cell Depletion in Peripheral Blood, Bone Marrow and Lymph Nodes of Systemic Lupus Erythematosus

Ioanna Minopoulou¹, Olaf Penack², Fredrik Albach¹, Artur Wilhelm³, Arnd Kleyer⁴, Dominic Borie⁵, Vincent Casteleyn¹, Robert Biesen¹, Philipp Enghard⁶, Thomas Dörner⁷, Norman Drzeniek⁸, Jan Zernicke¹, Tobias Alexander³, Kamran Movassaghi², Marie Luise Hütter-Krönke⁹, Eva Schrezenmeier⁶, Adrian Schreiber¹⁰, udo schneider¹, Lars Bullinger¹¹, Gerhard Krönke¹² and David Simon¹³, ¹Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, Berlin, Germany, ²Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany, Berlin, Germany, ³Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany/ Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany, Berlin, Germany, ⁴Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany/ Department of Internal Medicine 3, University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany/ Deutsches Zentrum für Immuntherapie (DZI), University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany, Berlin, Germany, ⁵Kyverna Therapeutics, Inc., Emeryville, CA, ⁶Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany/ Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany, Berlin, Germany, ⁷Department of Medicine, Rheumatology and Clinical Immunology,Charite Universitätsmedizin Berlin, Germany and DRFZ, Berlin, Berlin, Germany, ⁸Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany/ Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany/ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany/Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Immunology, Berlin, Germany, Berlin, Germany, ⁹Department of Hematology, Oncology and Cancer Immunology, Charité University Medicine Berlin, Campus Steglitz, Berlin, Germany, Berlin, Germany, ¹⁰Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany, Berlin, Germany, ¹¹Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany/ Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, Berlin, Germany, ¹²Rheumatology, Charité, Berlin, Germany, ¹³Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany/ Department of Internal Medicine 3, University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany/Deutsches Zentrum für Immuntherapie (DZI), University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany, Berlin, Germany

Meeting: ACR Convergence 2024

Keywords: B-Lymphocyte, Systemic lupus erythematosus (SLE), T Cell

Session Information

Date: Monday, November 18, 2024

Title: SLE – Treatment Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Anti-CD19 chimeric antigen receptor (CAR) T cells have emerged as a promising therapeutic option for treatment-refractory patients with B cell-mediated diseases such as systemic lupus erythematosus (SLE) (Mackensen A et al. Nat Med 2022, Müller F et al. NEJM 2024). Anti-CD19 CAR T cells trigger a rapid B cell depletion in the peripheral blood and simultaneously induce clinical remission. However, the effect of anti-CD19 CAR-T cell therapy in the bone marrow and lymph nodes of SLE patients has not yet been investigated.

Methods: A 46-year-old male patient with severe, treatment-refractory SLE underwent autologous anti-CD19 CAR T cell therapy with KYV-101 following lymphodepletion with fludarabine (15mg/m²due to impaired kidney function) and cyclophosphamide (300mg/m²). Whole blood samples were obtained before and after anti-CD19 CAR T cell therapy. Additionally, bone marrow and inguinal lymph node biopsies were performed 16 weeks post-treatment. B and T cell immune phenotyping were conducted using flow cytometry.

Results: Significant clinical improvement was observed 16 weeks after anti-CD19 CAR T cell infusion (SLEDAI 2K score reduction of 10 points from baseline), despite cessation of other immunosuppressive therapies. Peripheral blood B cells dramatically decreased and remained absent through week 16 post-treatment (Figure 1a) while anti-CD19 CAR T cells remained detectable (Figure 1b). Similarly, B cells and particularly CD19⁺ plasmablasts and CD19⁺ plasma cells in the bone marrow were significantly diminished at week 16, with the few detected B cells exhibiting a naïve phenotype (CD27^–CD38^– B cells) (Figure 2a). Anti-CD19 CAR T cells persisted in the bone marrow, where we observed an even distribution between CD4⁺ and CD8⁺ CAR T cells. Most of them exhibited high PD-1 expression, indicating exhaustion (McLane L et al. Annu Rev Immunol 2019) (Figure 2b). No B cells were detected in the lymph node at week 16 post-treatment (Figure 3a) and anti-CD19 CAR T cells were also rare (Figure 3b).

Conclusion: In SLE, anti-CD19 CAR T cell therapy enables broad, tissue-based depletion of B cells in the peripheral blood, bone marrow and lymph nodes 16 weeks post-treatment. These findings support the notion that anti-CD19 CAR T cell therapy induces remission in patients with SLE through complete and sustained depletion of autoreactive B cells within primary and secondary lymphatic organs.

Figure 1. a. Representative dot plots showing FACS analysis of B cells from the peripheral blood before and after 16 weeks of anti-CD19 CAR T cell therapy stained with anti-CD38 and anti-CD27. b. Dot plots of FACS staining of peripheral blood anti-CD19 CAR T cells for CD4, CD8, PD_1 (as a marker of T cell exhaustion) and CD69 (as a marker of T cell activation) at week 16 post-treatment.

Figure 2.a. Representative dot plots depicting FACS analysis of B cells from the bone marrow 16 weeks post-treatment stained with anti-CD14, anti-CD19, antiCD38 and anti-CD27. b. Dot plots of FACS staining of bone marrow anti-CD19 CAR T cells for CD4, CD8, PD_1 (as a marker of T cell exhaustion) and CD69 (as a marker of T cell activation) at week 16 post-treatment.

Figure 3.a. Dot plots illustrating FACS analysis of B cells from the lymph node 16 weeks post-treatment stained with anti-CD14, anti-CD19, antiCD38 and anti-CD27. b. Dot plots of FACS staining of lymph node anti-CD19 CAR T cells for CD4, CD8, PD_1 (as a marker of T cell exhaustion) and CD69 (as a marker of T cell activation) at week 16 post-treatment.

Disclosures: I. Minopoulou: None; O. Penack: None; F. Albach: None; A. Wilhelm: None; A. Kleyer: None; D. Borie: Kyverna Therapeutics, Inc., 3; V. Casteleyn: None; R. Biesen: None; P. Enghard: None; T. Dörner: AbbVie, 2, 5, Celgene, 2, 5, Deutsche Forschungsgemeinschaft, 5, Eli Lilly, 2, 5, EMD Merck Serono, 2, 5, EU Horizon 2020 HarmonicSS, 5, Gilead/Galapagos, 2, GSK, 2, 5, Janssen, 2, 5, Novartis, 2, 5, Roche/GNE, 2, 5, Sanofi, 5, UCB Pharma, 5; N. Drzeniek: None; J. Zernicke: None; T. Alexander: None; K. Movassaghi: None; M. Hütter-Krönke: None; E. Schrezenmeier: None; A. Schreiber: None; u. schneider: None; L. Bullinger: None; G. Krönke: Kyverna Therapeutics Inc, 5, 6; D. Simon: None.

To cite this abstract in AMA style:

Minopoulou I, Penack O, Albach F, Wilhelm A, Kleyer A, Borie D, Casteleyn V, Biesen R, Enghard P, Dörner T, Drzeniek N, Zernicke J, Alexander T, Movassaghi K, Hütter-Krönke M, Schrezenmeier E, Schreiber A, schneider u, Bullinger L, Krönke G, Simon D. Anti-CD19 Chimeric Antigen Receptor T Cell Therapy Induces Multicompartmental B Cell Depletion in Peripheral Blood, Bone Marrow and Lymph Nodes of Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/anti-cd19-chimeric-antigen-receptor-t-cell-therapy-induces-multicompartmental-b-cell-depletion-in-peripheral-blood-bone-marrow-and-lymph-nodes-of-systemic-lupus-erythematosus/. Accessed .

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