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

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). 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. 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 achieved an SRI-4 response at 6 months, with 6 patients meeting LLDAS criteria and 5 achieving DORIS remission. Improvements in renal function and complement levels were also noted. Relma-cel demonstrates a manageable safety profile and promising efficacy in patients with moderately to severely active SLE. A dose of 100 × 10 6 CAR-T cells was identified as the recommended phase II dose based on clinical response and tolerability. • First clinical evaluation of relma-cel, a CD19 CAR-T cell product, in patients with active SLE. • Relma-cel showed consistent expansion and durable B-cell depletion in SLE. • Fixed-dose relma-cel (50–100×10⁶) was well tolerated with no DLTs or severe CRS/ICANS. • Relma-cel improved multiple endpoints, including SRI-4, LLDAS, and DORIS remission.