Abstract: SA-OR100
Safety and Efficacy of Low-Dose CD19-Targeted CAR T Cells in Refractory Pediatric Systemic Lupus Erythematosus (SLE)
Session Information
- Late-Breaking Science Orals - 2
October 26, 2024 | Location: Room 6C, Convention Center
Abstract Time: 05:00 PM - 05:10 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Li, Qiu-yu, Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- He, Xue, Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Zhang, Yingzi, Chongqing Precision Biotech Co., Ltd., Chongqing, China
- Liu, Fei, Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Wang, Jingjing, Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Mao, Jianhua, Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
Background
Recent advancements indicate that CAR T cell therapy shows promise for treating SLE, there remains a significant lack of data in pediatrics. This study evaluates the safety and efficacy of CAR T-cell therapy in pediatric SLE by utilizing autologous CD19-targeted CAR T cells (MC-1-50) to treat refractory pediatric SLE.
Methods
In this Phase I/II study (NCT06222853), MC-1-50 CAR T cells were manufactured by the PRIMCAR manufacturing platform. Most patients(pts) were preconditioned with fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) daily for 3 days, while some received dosage reduction due to infections or intolerance. Toxicity was graded by CTCAE V5.0, CRS and ICANS were graded by ASTCT criteria.
Results
AS of August 2024, 11 pts were infused with MC-1-50 (Table). 9 pts (81.8%) experienced CRS, all at grade 1. 2 pts (18.2%) experienced grade 1 ICANS. There were no unexpected adverse events (AE) or seriou AE reported. 5 pts were followed for over 3 months (3M), with 4 achieving SRI-4 response. Notably, for Pt 5, though there was persistent proteinuria at 3M, all other active indicators had normalized, and her scr levels had declined from a peak of 786 to 169μmol/L, accompanied by a urine output from 50-100ml/day to 1000mL/day. The other pts exhibited varying degrees of improvement. CAR T cells expansion was observed in all dose levels, and B cells were rapidly eliminated within 7 days after infusion while its reconstitution was observed in most pts by 2M. It was noted that the majority of these B cells were predominantly naive B cells.
Conclusion
The treatment of refractory pediatric SLE with a low dose of CD19-targeted CAR-T Cells (MC-1-50) demonstrated an excellent safety profile while exhibiting high efficacy.
Disease characteristics and safety outcomes.
| ID | Age | Gender | Duration of disease(Years) | Kidney biopsy | Dose | CRS | ICANS | Follow-up period | SLEDAI-2K Baseline | SLEDAI-2K at present |
| PBC053-001 | 12 | F | 3 | / | 1×10^5/kg | 1 | 1 | 5M | 12 | 0 |
| PBCP53-002 | 12 | F | 5 | LN-IV | 1×10^5/kg | 1 | / | 4M | 12 | 8 |
| PBC053-003 | 12 | M | 5 | / | 1×10^5/kg | 1 | / | 3M | 16 | 0 |
| PBC053-004 | 17 | F | 11 | / | 0.3×10^5/kg | 1 | / | 3M | 12 | 2 |
| PBC053-005 | 15 | F | 2 | LN-IV | 1×10^5/kg | / | / | 2M | 12 | 4 |
| PBC053-006 | 15 | F | 7 | LN-IV+V | 1×10^5/kg | 1 | / | 2M | 18 | 6 |
| PBC053-007 | 15 | F | 6 | LN-IV | 1×10^5/kg | / | / | 1M | 12 | 8 |
| PBC053-008 | 19 | F | 9 | / | 3×10^5/kg | 1 | 1 | 1M | 23 | 6 |
| PBC053-010 | 6 | F | 2 | LN-V | 3×10^5/kg | 1 | / | 14D | 10 | 6 |
| PBC053-011 | 11 | F | 0.4 | LN-II | 0.3×10^5/kg | 1 | / | 14D | 12 | 8 |
| PBC053-012 | 13 | F | 5 | LN-IV | 0.3×10^5/kg | 1 | / | 14D | 8 | 8 |
Funding
- Other NIH Support – Chongqing Precision Biotech Co., Ltd.