BCMA-CD19 armored compound CAR T cells in systemic lupus erythematosus: extended follow-up of a phase 1 clinical trial
Ming Hong, Mingxia Wang, Ronghao Zeng, Ling Ding, Shanzhi He, Ting Lan, Vincent M DeStefano, Masayuki Wada, Kevin G. Pinz, Jennifer E. Chow, Byeong Hyeok Choi, Nabil Hagag, Min Wang, Yu Ma, Jing Luo, Yingwen Liang, Shihao Ding, Ziji Lu, Wenli Zhang, Yupo Ma, Weijia Wang
Abstract
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.