Poster Session C
Systemic lupus erythematosus (SLE)
Ioanna Minopoulou, MD,MSc
Universitätsmedizin Charite Berlin
Berlin, Germany
No financial relationships with ineligible companies to disclose
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/m2 due 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.
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.