Dual-target CAR T therapy for refractory SLE
Feng J, Huo D, Hong R, et al. Co-Infusion of CD19-Targeting and BCMA-Targeting CAR-T Cells for Treatment-Refractory Systemic Lupus Erythematosus: A Phase 1 Trial. Nature Medicine. 2025; (doi: 10.1038/s41591-025-03937-8).
Early Phase I study results demonstrate the promise of chimeric antigen receptor (CAR) T-cell therapy targeting both CD19 and BCMA cells in patients with systemic lupus erythematosus and inadequate response to conventional immunosuppression. Participants in the dose-escalation trial received coinfusion of autologous anti-CD19 and anti-BCMA CAR T cells. Dose-limiting toxicities within 28 days, a coprimary outcome, were absent in all 15 patients included in the interim reporting. The other main endpoint was adverse events (AEs) within 12 weeks, which suggested an overall favorable safety profile. The top grade 3 or higher AEs — neutropenia, which affected all 15 patients, plus thrombocytopenia and anemia — were reversible with supportive care. While cytokine release syndrome affected 86.7% of participants, the complication presented as grade 1 and was not associated with neurotoxicity or treatment-related mortality. Remission was achieved in 12 of 15 patients by week 12, the study authors report, and sustained eradication of pathogenic clones in 3 patients followed for 1 year suggests that coinused CAR T treatment is potentially curative.