POS0061 BCMA-CD19 DUAL-TARGETING CAR-T CELL FOR THE TREATMENT OF REFRACTORY THROMBOCYTOPENIA ASSOCIATED WITH AUTOIMMUNE DISEASES

<h2>Abstract</h2><h3>Background:</h3> Immune thrombocytopenia (ITP) can be secondary to various autoimmune diseases (AIDs). Patients with refractory thrombocytopenia often have high risk of fatal visceral bleeding events associated with a poor prognosis. Autoantibodies produced by B and plasma/long-lived plasma cells are at the "root cause" of ITP pathogenesis. Our novel BCMA-CD19 dual-targeting CAR-T therapy (cCAR) comprehensively targets both humoral cell types responsible thrombocytopenia in ITP associated with AIDs. <h3>Objectives:</h3> To evaluate the safety and efficacy of cCAR in patients with refractory thrombocytopenia associated with autoimmune diseases. <h3>Methods:</h3> An phase I open-label, single arm, single center study (IRB number:2023-1610) to evaluate the safety, efficacy of BCMA-CD19 dual-targeting CAR-T in patients with refractory thrombocytopenia associated with autoimmune diseases in China is currently ongoing. Following the lymphodepleting therapy of cyclophosphamide 500mg/m²/day, patients were dosed with 0.5-1.0×10⁶ CAR-T cells/kg body weight. Efficacy was determined by platelet count and anti-platelet antibody levels. We recorded any adverse event (AEs) and serious adverse events (SAEs), including the cytokine release syndrome （CRS） and neurotoxicity (NT). We monitored CAR-T cell kinetics by flow cytometry. <h3>Results:</h3> Between August and December 2024, 4 patients with refractory thrombocytopenia associated with AIDs received CD19-BCMA dual-targeting CAR-T cells treatment, including 1 patients with systemic lupus erythematosus and 3 patients with undifferentiated connective tissue disease (UCTD). Safety, pharmacokinetics (PK) and preliminary efficacy data for the first three patients who received treatment, and acute safety data for all five patients who received treatment (data cutoff: 10 Jan 2025) are presently available. All patients were female, aged between 32 and 48 years. All patients previously exposed to high dose steroids, Hydroxychloroquine, immunosuppressive drugs (Cyclosporine, Mycophenolate mofetil, Tacrolimus), Intravenous immunoglobulin (IVIg), biological agents (rituximab, telitacicept, beliuzumab) and thrombopoietin receptor agonists. Bone marrow biopsies confirmed the diagnosis of immune thrombocytopenia and clonal haematopoiesis was excluded. After CAR-T cells infusion, transient lymphodepletion-related cytopenia (grade 3 or 4) was observed in all 4 patients as expected. Neutropenia (grade 3) was observed in all 4 patients, however, this recovered within 2 weeks with supportive care. Cytokine release syndrome (CRS) was observed in all 4 patients. All CRS events were grade 1. Tocilizumab was administered in 2 patients. No events of immune cell-associated neurotoxicity syndrome or infectious complications were reported. Following BCMA-CD19 dual targeting CAR-T therapy, platelet count returned to normal （>100×10⁹/L） in all patients. P2's platelet count initially increased into the normal range, however, decrease to slightly below normal limits by day 42 post-cCAR (Detailed data are shown in the Figure 1). Complete B cell depletion were observed (0cells/μL) by day4-11, and recovery of B cells is being monitored with P1 demonstrating recovery by day 84. The nadir of B concertation was observed from day 7-28 and then starting recovery at day 56. CAR-T cell expansion with a median peak concentration (Cmax) of 806 cells/μL by flow cytometry and Tmax between 7-14 days post infusion. Figure 1 <h3>Conclusion:</h3> Preliminary data from the first 4 patients suggested favorable profiles on safety and efficacy with our novel BCMA-CD19 dual-targeting CAR-T therapy. Remarkable short-interval resolution of thrombocytopenia to date (all patients by day 14 post-cCAR) is encouraging. No severe toxicity has been observed to date. Additional patients and the corresponding date will be presented at the meeting. <h3>REFERENCES:</h3> [1] Caël B, Bôle-Richard E, Garnache-Ottou F, et al. CAR-T cell therapy: recent updates and challenges in autoimmune diseases. J Allergy Clin Immunol. 2024 Dec 13:S0091-6749(24)02354-6. doi: 10.1016/j.jaci.2024.12.1066. <h3>Acknowledgements:</h3> <b>NIL</b>. <h3>Disclosure of Interests:</h3> Min Yang: None declared, Tao Liu: None declared, Bo Chen: None declared, Wei Lin: None declared, XiaoMin Cen: None declared, Hua Zhao: None declared, Vincent DeStefano iCell Gene Therapeutics Inc, Jing Luo iCar Bio Therapeutics Ltd, Yu Ma iCar Bio Therapeutics Ltd, Yupo Ma iCell Gene Therapeutics Inc, Qibing Xie: None declared. © 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.