Autologous CD19 CAR-T cell therapy for pediatric and adult systemic lupus erythematosus: A phase 1/2 trial.
Level 4 - case-series / case-control
Single-arm uncontrolled phase 1/2 clinical trial
PubMed 41935952 · doi:10.1016/j.ymthe.2026.03.037
What was done
An open-label phase 1/2 trial evaluated autologous CD19 CAR-T cell therapy in 18 patients with systemic lupus erythematosus (SLE; 15 pediatric, 3 adult; 15 with baseline SLEDAI-2K ≥4 and 3 with <4). Dose allocation used a time-to-event Bayesian optimal interval design. 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.
What was found
No DLT occurred; the recommended phase 2 dose was 1 × 10^6 CAR-T cells/kg. AEs included grade 1 cytokine release syndrome in 72% of patients, neurotoxicity in 17%, and grade 1–2 infections in 17%. Among the 15 patients with baseline SLEDAI-2K ≥4, SRI-4 response was achieved by 9 patients at month 3 and 12 at month 6; 1 patient achieved lupus low disease activity state at month 6, and 2 were non-responders. All 3 patients with baseline SLEDAI-2K <4 achieved definition of remission in SLE. Over 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, accompanied by transient B cell ablation.
Why it matters
This study provides early evidence that autologous CD19 CAR-T cell therapy is safe and can induce drug-free clinical responses in patients with SLE, particularly in pediatric cohorts.
Limits
The study is limited by a small sample size (n = 18), lack of a control or comparator arm, and a predominantly pediatric population (15/18) limiting generalizability to adults. The median follow-up of 10.2 months is too short to establish long-term durability or late safety outcomes.