[Long-term follow up of efficiency and safety of CD19-CAR T-cell treatment of systemic lupus erythematosus].

BACKGROUND

Chimeric antigen receptor T-cells (CAR T-cells) are an effective therapeutic approach in the treatment of B-cell driven malignancies. In addition to malignant B-cells, autoreactive B-cells are important targets for CD19 CAR T-cells, as they are a source of autoantibody production and support both the onset and progression of systemic lupus erythematosus (SLE). We and others have shown that their use in severe and therapy-refractory cases of SLE is effective and, moreover, safe.

OBJECTIVE

The current status and an interim analysis of the efficacy and safety of CD19-CAR T‑cell therapy in SLE.

MATERIAL AND METHODS

Patients with severe, treatment-refractory, and active SLE received autologous CD19-CAR T‑cell therapy (MB19.1, Miltenyi Biotec, Bergisch Gladbach, Germany) as part of an individual compassionate treatment attempt and are regularly followed up at our center.

RESULTS

11 patients with progressive, therapy-refractory SLE received an autologous CD19 CAR T-cell therapy as part of an individual treatment attempt. The median follow-up time is 2.5 years [0.5 - 4 years]. All patients achieved a DORIS remission within 6 months. Immunosuppressive therapy was completely discontinued in all patients. Five out of the 11 patients experienced grade 1 cytokine release syndrome (CRS). Grade 2 CRS was observed only once. No higher-grade CRS occurred in this cohort. So far, no neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS) has been observed in our SLE patients. All patients remain in a sustained and drug-free remission to date. One patient experienced an SLE flare. Initial data, despite similar CD19 CAR T-cell expansion and kinetics, suggest a better safety profile of CD19 CAR T-cell therapy in SLE compared to lymphoma cohorts. Additionally, adaptive immunity in SLE patients recovers rapidly after CD19 CAR T-cell therapy.

CONCLUSION

The use of CD19-CAR T‑cells in patients with severe SLE proved to be safe and effective.