Poster Session A
Systemic lupus erythematosus (SLE)
Greg Deener, BS
iCell Gene Therapeutics Inc.
Henrico, Virginia, United States
No financial relationships with ineligible companies to disclose
cCAR approved by Zhongshan People’s Hospital, Peking University Shenzhen Hospital IRBs for autoimmune patients. cCAR achieved CR in both SLE/lymphoma, IRB then approved cCAR for use in LN (11 LN patients June 22 to Feb 23, 10 at target dose 3 x 106/kg). The 2 SLE/lymphoma and 10 LN target dose patients comprise efficacy population. 18 patients in safety dataset. Lupus patients: All SLE medications discontinued after apheresis and prior to cy only (LN) or cy/flu (SLE/lymphoma) conditioning. Patients dosed with cCAR and monitored. LN: required to fail multiple lines of therapy with active disease on kidney biopsy (class III to V). All LN/SLE patients met ACR criteria. Complete Remission definition: both DORIS remission criteria (clinical SLEDAI = 0, SELENA-SLEDAI Physician Global Assessment (PGA) ≤0.5, no glucocorticoids, no immunosuppressants and no biologics) and no serology (no elevated autoantibodies/normal complement). No active disease in SELDAI-2K patients with proteinuria >0.5 g/24-hours if both no serology past 6 months and biopsy confirming no active disease.
Baseline Characteristics: Efficacy population: age range: 17-58, 10 of 12 female. SLEDAI-2K baseline mean = 9.5. All LN patients at screening treated with HCQ, glucocorticoid, immunosuppressant; majority with belimumab. At screening, LN patients mean 24-hour urine microprotein 1.7g, urine/creatine ratio 1.0. 10 LN patients total of 38 elevated autoantibodies (24 >3X ULN). Majority had low C3.
Results:
Safety: cCAR well tolerated; no CRES/ICANS, no CRS >grade 1. Among LN target dose patients: only infection other than Covid-19 was a grade 1 UTI; B cells, IgM, and IgA normal in all patients, IgG >400 mg/dL in all patients (7/10 normal; 3 not yet normal were low at screening).
Complete Remission: Mean follow-up of 20 months in efficacy population, 11 of 12 patients in Complete Remission. Among all 12 patients: no elevated autoantibodies, normal complement, score of 0 on PGA, and no SLE medications. 11 of 12 with score of 0 on SLEDAI-2K. One patient scores 4 on SLEDAI-2K in proteinuria likely due to prior damage (no elevated autoantibodies, complement normal), but has not yet had a rebiopsy. 2nd patient has proteinuria >0.5 g/24-hour and had a rebiopsy demonstrating no active disease with normal complement/no elevated autoantibodies for >18 months. Among 10 LN patients at target dose, 7 achieved a complete renal response and 1 had a partial renal response. The 9 patients scoring 0 on SLEDAI-2K average an -85% reduction in proteinuria from screening (on SLE meds).
Conclusion:
BCMA-CD19 cCAR can safely achieve long-term medication-free Complete Remission. Will update dataset at ACR. Further research needed.
Y. Yuan: None; S. He: None; W. Zhang: None; H. Zhang: None; V. DeStefano: iCell Gene Therapeutics, Inc., 3; M. Wada: iCell Gene Therapeutics, Inc., 3; K. Pinz: iCell Gene Therapeutics, Inc., 3; G. Deener: iCell Gene Therapeutics, Inc., 4; Y. Ma: iCAR Bio Therapeutics, Ltd, 3; M. Wang: None; F. Li: None; M. Hong: None; C. Zou: None; M. Wang: None; L. Ding: None; Y. Liang: None; Y. Ma: iCell Gene Therapeutics, Inc., 4; W. Wang: None.