Co-infusion of CD19-targeting and BCMA-targeting CAR-T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial.
Fifteen patients with severe lupus that had failed standard treatment received engineered immune cells targeting two different markers on antibody-producing cells. Most reached remission by 12 weeks and stayed off lupus drugs, with side effects that were manageable.
Background
A subset of patients with systemic lupus erythematosus remains refractory to conventional immunosuppression. The investigators showed that peripheral CD19+ B cells and bone marrow CD19-BCMA+ long-lived plasma cells are both dominant autoantibody sources, providing the rationale for dual CD19 and BCMA targeting rather than CD19 alone.
Study design
Fifteen patients (14 female, one male) received co-infused autologous anti-CD19 and anti-BCMA CAR-T cells after fludarabine/cyclophosphamide lymphodepletion in a dose-escalation design. Primary endpoints were dose-limiting toxicities within 28 days and adverse events within 12 weeks; secondary endpoints included LLDAS and DORIS remission at 12 weeks and CAR-T persistence to 24 weeks. Median follow-up was 712 days (range 613-1,134).
Key findings
No dose-limiting toxicities occurred. By week 12, 12 of 15 patients (80%) met both LLDAS and DORIS remission criteria. Multiomic analyses confirmed elimination of autoreactive CD19+BCMA+ clones, reconstitution of naive IgM/IgD B cells, and durable downregulation of interferon-stimulated and BAFF-dependent signatures. Three patients monitored for one year showed sustained eradication of pathogenic clones.
Safety
Grade 1 cytokine release syndrome developed in 86.7% of patients, with no neurotoxicity and no treatment-related deaths. The most common grade 3 or higher adverse events were neutropenia (100%), thrombocytopenia (40%) and anaemia (13.3%), all reversible with supportive care.
Clinical implications
For nephrologists managing refractory lupus nephritis, dual-target CAR-T is now a credible referral pathway to consider at specialist centres, though the evidence remains phase 1 in scale. Patient selection, lymphodepletion tolerance and cytopenia management are the practical gatekeepers.
Category
Research
Source
Nature Medicine
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