BCMA-CD19 armored compound CAR T cells in systemic lupus erythematosus: extended follow-up of a phase 1 clinical trial

CD19 CAR T-cells have shown promise in treating systemic lupus erythematosus (SLE), however, relapses demonstrate persistently elevated autoantibodies characteristic of CD19-negative long-lived plasma cells (LLPCs). Alternatively, ICG318, a dual-targeting BCMA-CD19 armored CAR T-cell therapy, targets both B cells and plasma cells/LLPCs driving SLE which may improve outcomes. Herein, we present 12 patients with refractory SLE, including 10 with lupus nephritis (LN), who received ICG318 CAR T-cells resulting in 10 of 12 achieving stringent complete remission (sCR) defined by medication-free DORIS CR and complete renal response (CRR). Eleven of 12 achieved drug-free, serological CR. Nine patients underwent repeat renal biopsy demonstrating evidence of remarkable histological improvement with clearance of immune-complex deposits and resolution of chronic glomerular injury. The safety profile was favorable, with no high-grade cytokine release syndrome or neurotoxicity. Notably, successful spontaneous pregnancies and births of healthy full-term infants occurred post-treatment, warranting future study of fertility outcomes. sCR approaching 6 years raises the possibility of a long-term durable response to CAR T-cell therapy in humoral autoimmune disease.