OP0279 CAR-T CELL TREATMENT OF REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS- SAFETY AND PRELIMINARY EFFICACY DATA FROM THE FIRST FOUR PATIENTS

Background While treatment of Systemic lupus erythematosus (SLE) has substantially improved, a subset patients experiences severe progressive disease despite T- and B cell targeted therapy. Furthermore, drug-free remission seroconversion is difficult to achieve in SLE date Objectives To study the safety, tolerability, preliminary efficacy deep depletion using autologous CD19 chimeric antigen receptor (CAR) T cells with treatment-refractory Methods The CAR product was manufactured by CliniMACS Prodigy system (Miltenyi Biotec, Bergisch Gladbach, Germany). T-cells were enriched from patients’ peripheral blood apheresis 1x10 8 used as starting population. transfected lentiviral vector encoding an anti-CD19 composed FMC63 scFv, CD8- derived hinge region, TNFRSF19-derived transmembrane domain, CD3ζ intracellular 4-1BB co-stimulatory domain Biotec) expanded for 12 days. After conditioning cyclophosphamide/ fludarabine received 6 CD19-CAR-T cells/kg body weight single infusion. All treatments exception low dose prednisolone stopped before CAR-T administration. treatment, also stopped. Tolerability assessed monitoring Cytokine-release syndrome (CRS), immune-related effector neurotoxicity (ICANS) infections. Preliminary reaching Lupus Low Disease Activity State (LLDAS), dsDNA antibodies ANA cessation all SLE-specific Results As January 22, 2022, our 4 had been treated follow up 10 months (patient 1, female aged 20, SLEDAI-2K: 16), 7 2, male 22; SLEDAI-2K:8), 2 3, SLEDAI 2K: 6), 1 month 4; 24; respectively. active failure standard including pulsed steroids, hydroxychloroquine, mycophenolate, cyclophosphamide, intravenous immunoglobulins, rituximab belimumab kidney disease. No infections occurred. four experienced fever without proof infectious (CRS °I); only one patient tocilizumab. ICANS no CRS other organs In vivo, rapidly maximum 27,6% (day 9, 1), 41,2% 2), 11,5% 3) 59,1% 4) total circulating followed typical decline, being continuously detectable during next months. Expansion preceded complete sustained cells. Patient (SLEDAI-2K=0) loss reappearance at not yet returned. Low-level proteinuria remained most likely due previously accrued damage glomerular filter function (SLEDAI-2K: 2). 3 shorter observation period but achieved clinical (both SLEDAI-2K 0). met LLDAS could successfully stop medication, glucocorticoids. flare occurred so far. Conclusion Taken together, these data show that T-cell therapy well tolerated may induce rapid refractory SLE. References [1]Mougiakakos D et al., CD19-Targeted Cells Refractory Erythematosus. N Engl J Med 2021;385:567-569. Disclosure Interests None declared