Background/Purpose: Medication free complete remission (CR) has been elusive in SLE. An open label investigator-initiated trial (IIT) infused SLE/LN patients with a novel cCAR targeting BCMA and CD19. Complete humoral reset defined as elimination of both B cell memory (CD19) and autonomous long-lived plasma cell memory (BCMA). Patients evaluated for safety and durable CR using DORIS criteria plus absence of serology.

Methods: 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.  

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bcma-cd19-compound-car-t-ccar-safely-provides-a-complete-humoral-reset-eliminating-all-autoantibodies-resulting-in-long-term-medication-free-complete-remission-among-systemic-lupus-erythematosus-sl/