[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.