CARLYSLE phase I trial: Obe-cel for severe, refractory SLE

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Claire Roddie presented preliminary efficacy and safety data from the phase I CARLYSLE trial (NCT06333483) of obecabtagene autoleucel (obe-cel), a CD19-targeting chimeric antigen receptor (CAR) T-cell therapy, in nine patients with severe, refractory systemic lupus erythematosus (SLE). Patients received obe-cel 50 × 10⁶ (50M cohort, n = 6) or 100 × 10⁶ (100M cohort, n = 3) CAR T-cell infusion. Key endpoints included dose-limiting toxicities (DLTs), adverse events (AEs), and Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) remission.  

Key data: No DLTs, immune effector cell-associated neurotoxicity syndrome (ICANS), or Grade ≥2 cytokine release syndrome (CRS) events occurred. In the 50M cohort, 83.3% of patients (5/6) achieved DORIS remission at a median onset of 5.1 months; 50.0% (3/6) of patients achieved a complete renal response (CRR) at Month 1. Clinically meaningful SLE Disease Activity Index 2000 (SLEDAI-2K) reductions were observed in both cohorts. In the 50M and 100M cohorts respectively, the median time to CAR T-cell persistence loss was 3.0 and 2.0 months, while the median time to B-cell recovery was 6.0 and 5.8 months . 

Key learning: Preliminary findings demonstratea favorable safety profile, pronounced CAR T-cell expansion, and observed clinical benefit, suggesting that obe-cel could offer a potential treatment option for patients with severe, refractory SLE.