Preliminary safety and efficacy of relmacabtagene autoleucel (relma-cel) in adults with moderately to severely active systemic lupus erythematosus: a phase I dose-escalation study

作者：Yiyang Wang, Shaoying Yang, Ye Yu, Peng Xia, Cui-Wei Xie, Chunyan Zhang, Liangjing Lu · 发表于：Journal of Autoimmunity · 年份：2025 · DOI：10.1016/j.jaut.2025.103489 · 被引用次数：7 · 研究领域：CAR-T cell therapy research、Systemic Lupus Erythematosus Research、Biosimilars and Bioanalytical Methods

Background Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative treatment in autoimmune diseases. Relmacabtagene autoleucel (relma‐cel) is an autologous, CD19-directed CAR-T cell product developed with a commercial-ready process in China. This study evaluates the safety and efficacy of relma‐cel in patients with moderately to severely active systemic lupus erythematosus (SLE). Methods In this phase I, single-arm, dose escalation study, 8 female patients with moderately to severely active SLE were enrolled. All patients received a single infusion of relma‐cel at escalating doses (50 × 10 6 , 75 × 10 6 , or 100 × 10 6 CAR-T cells) after preconditioning with fludarabine and cyclophosphamide. The primary endpoints included the incidence of dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs). Secondary endpoints comprised pharmacokinetics, pharmacodynamics, and efficacy, which was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), SLE Responder Index (SRI)-4, Lupus Low Disease Activity State (LLDAS), and Definition of Remission in SLE (DORIS) remission criteria. Results No dose-limiting toxicities were reported. Adverse events were manageable, with cytokine release syndrome (CRS) occurred in 7 patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 1 patient. The mean SLEDAI-2K score of patients decreased from 12.625 at baseline to 3.25 at follow-up. All patients a...