Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with multisystem involvement. A subset of patients remains refractory to glucocorticoids, conventional immunosuppressants, and biologic agents, resulting in relapsed/refractory SLE (r/r SLE), persistent disease activity, cumulative organ damage, and substantial treatment-related toxicity. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has shown the potential to induce deep B-cell depletion and immune reset in r/r SLE. However, the currently available evidence is mainly derived from case reports, small case series, and early-phase clinical studies, and is complicated by duplicate publications, follow-up extensions, and inconsistent outcome reporting. This study aimed to systematically synthesize the available clinical evidence on CAR-T therapy for r/r SLE, with a focus on efficacy, safety, and patient-level evidence patterns.

A systematic review of published original studies on CAR-T therapy in r/r SLE was performed. To avoid duplication of evidence, an “independent study unit” approach was applied to resolve overlapping publications, companion reports, and follow-up articles. A patient-level master dataset was then constructed. In total, 21 independent study units comprising 114 counted patients were included. Extracted variables included age, sex, major organ involvement, CAR target and product type, autologous versus allogeneic cell source, and safety outcomes such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection, and hypogammaglobulinemia. Efficacy endpoints included DORIS remission, Lupus Low Disease Activity State (LLDAS), SRI-4 response, drug-free remission, and renal outcomes. A descriptive integrated synthesis was conducted.

 The included patients were predominantly female, with a median age of approximately 32 years, and renal involvement was the most common disease phenotype. Treatment platforms included autologous CD19 CAR-T, autologous BCMA-related CAR-T, autologous CD19/CD22 dual-target CAR-T, allogeneic CD19 CAR-T, and allogeneic CAR-NK therapy. Overall, CAR-based therapy was associated with rapid and profound B-cell depletion, reduction in disease activity, and improvement in serological markers. Among patients with exact patient-level attribution, high rates of DORIS remission and SRI-4 response were observed, and a subset of patients achieved sustained drug-free remission without glucocorticoids or immunosuppressive agents. From a safety perspective, most CRS events were low grade, ICANS was uncommon, and severe infections were not frequent overall. However, severe inflammatory complications, including HLH-like syndromes and thrombotic microangiopathy, were observed in selected pediatric or high-inflammatory-burden settings. Early allogeneic platforms demonstrated promising tolerability and potential advantages in accessibility.

CAR-T cell therapy shows encouraging efficacy and an overall manageable safety profile in patients with r/r SLE, supporting its role as a potential immune-reset strategy in severe and treatment-resistant disease. By integrating patient-level evidence and correcting for duplicate publication streams, this review provides a more reliable picture of the current evidence landscape. Nevertheless, the available literature remains dominated by early-phase, non-randomized, small-sample studies with substantial heterogeneity. Larger prospective multicenter trials with standardized endpoint definitions, toxicity reporting, and immune reconstitution assessment are needed to clarify the optimal role of different CAR-T platforms in r/r SLE.