POS0946 IMMUNOCLEANSING-ASSOCIATED TOXICITY SYNDROME (ICATS) IN CAR T-CELL TREATED PATIENTS WITH AUTOIMMUNE DISEASE

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Background: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment strategies for severe B-cell driven autoimmune diseases (AID) like Systemic Lupus erythematosus (SLE), Systemic Sclerosis (SSc) or Idiopathic Inflammatory Myositis (IIM). Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and hematotoxicity are the most common and best described side effects, but little is known about AID-specific adverse events [1, 2]. Objectives: To describe a new form of toxicity - Immunocleansing-Associated Toxicity Syndrome (ICATS), related to the treatment of patients with autoimmune disease (AID) with CD19-targeting chimeric antigen receptor (CAR) T-cells. Methods: All AID patients receiving CAR T-cell therapy in Erlangen and Duesseldorf with a follow-up of at least 30 days were assessed for organ-specific ICATS. Observed reactions were documented according to localization, time, duration and graded for severity (grade 1: spontaneous resolution; grade 2: glucocorticoid use; grade 3: glucocorticoid use plus prolonged hospital stay; grade 4: intensive care treatment). No systemic events, such as fever, chills, nausea, fatigue, diffuse pain/hypersensitivity or hemodynamic changes were classified as ICATS to separate it from CRS. Furthermore, per definition, ICATS were time-limited events that spontaneously regressed or stopped after a short course of glucocorticoid treatment in order to distinguish it from recurrence of AID. Results: 39 patients with AID were treated with CD19-CAR T-cells (20 systemic lupus erythematosus, SLE; 13 systemic sclerosis, SSc; 6 idiopathic inflammatory myositis, IIM). 54 ICATS were recorded, affecting overall 30 patients (76.9%) with median (IQR) time of onset of 14 [5;21] days and a median duration of 11 [5;14] days (Table 1). ICATS exclusively occurred during the B-cell aplasia phase and only involved organs previously affected by the respective AID. Most frequent affected organs were the skin (N=19, 35.2%) and the kidneys (N=12, 22.2%). Most ICATS were mild (grade 1: 35, grade 2: 16). Only three ICATS were grade 3. All ICATS resolved without sequelae. Conclusion: ICATS is a new form of toxicity in CD19-CAR T-cell treated patients with AID, most likely based on the cleansing of immune cells from the affected organs. It is self-limited, organ-specific and usually mild in its intensity. REFERENCES: [1] Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med . 2024; 390:687-700. [2] Isaacs JD. CAR T Cells - A New Horizon for Autoimmunity?. N Engl J Med . 2024; 390:758-759. Table 1Demographics, Incidence and organ involvement of ICATS.SLEIIMSScTotalPatientsNumber of patients, N (%)20 (51.3)6 (15.4)13 (33.3)39Female, n (%)15 (75)5 (83.3)5 (38.5)25 (64-1)Age, years (median)3437,537,536Disease duration, years (median)322,53Number patients with ICATS, N (%)16 (80)4 (66.7)10 (76.9)30 (76.9)Number of events, N (%)34 (63)6 (11.1)14 (25.9)54Day of post CAR T-cells, days (median)13122014Duration of event, days (median)7141411Severity of eventsGrade 1, N (%)21 (61.8)3 (50)11 (78.6)35 (64.8)Grade 2, N (%)12 (35.3)2 (33.3)2 (14.3)16 (29.6)Grade 3, N (%)1 (2.9)1 (16.7)1 (7.1)3 (5.6)Grade 4, N (%)0000Organs InvolvedKidneys; N (%)11 (91.7)01 (8.3)12 (22.2)Skin, N (%)18 (94.7)01 (5.3)19 (35.2)Muscle, N (%)03 (60)2 (40)5 (8.8)Heart, N (%)002 (100)2 (3.5)Lungs, N (%)1 (33.3)1 (33.3)1 (33.3)3 (5.3)Gastrointestinal, N (%)003 (100)3 (5.3)Joints, N (%)4 (40)2 (20)4 (40)10 (18.5) Acknowledgements: NIL . Disclosure of Interests: Melanie Hagen BMS, Lilly, AlfaSigma, UCB, Biotest, Fabian Müller BMS, Cabaletta, Kyverna, Andreas Wirsching: None declared, Soraya Kharboutli: None declared, Silvia Spörl: None declared, Christina Duesing: None declared, Tobias Krickau: None declared, Markus Metzler: None declared, Simon Völkl: None declared, Michael Aigner: None declared, Sascha Kretschmann: None declared, Ingrid Vasova: None declared, Marc Saake: None declared, Stefan Schliep: None declared, Torsten Kubacki: None declared, Nicolas Hunzelmann: None declared, Laura Bucci: None declared, Jule Taubmann: None declared, Christina Bergmann: None declared, Andrea-Hermina Györfi: None declared, Sascha Dietrich: None declared, Jörg Distler: None declared, Ricardo Grieshaber-Bouyer: None declared, Andreas Mackensen BMS, Century Therapeutics Celgene, Kyverna, Gilead, Janssen, Miltenyi, and Novartis, Georg Schett BMS, Cabaletta, Janssen, Kyverna, Miltenyi, and Novartis. © 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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