Autologous CD19 CAR-T cell therapy for pediatric and adult systemic lupus erythematosus: A phase 1/2 trial

Clinical evidence regarding chimeric antigen receptor (CAR) therapy for systemic lupus erythematosus (SLE) remains limited. Here, we report a phase 1/2 trial evaluating the safety and efficacy of autologous CD19 CAR-T therapy. This study includes dose escalation and expansion stages, utilizing time-to-event Bayesian optimal interval phase 1/2 design for assigning doses based on benefit-risk trade-off. Primary endpoints were dose-limiting toxicity (DLT) within 28 days and adverse events (AEs) within 30 days in phase 1 and overall response rate at months 3 and 6 in phase 2. Eighteen patients, predominantly pediatric (n = 15), including 15 with Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) ≥4 were enrolled. No DLT occurred, and the recommended dose for phase 2 was 1 × 10⁶ CAR-T cells/kg. AEs included grade 1 cytokine release syndrome in 72%, neurotoxicity in 17%, and grade 1-2 infections in 17%. At months 3 and 6, of 15 patients with baseline SLEDAI-2K ≥4, 9 and 12, respectively, achieved SRI-4 response, 1 achieved lupus low disease activity state at 6 months, and 2 were non-responders. Three with baseline SLEDAI-2K <4 achieved definition of remission in SLE. With a median follow-up of 10.2 months, all responders maintained response without immunosuppressants, except for 1 relapse. CAR-T cells persisted for a median of 56 days and ablated B cells transiently. This approach shows safety and preliminary efficacy.