An interesting correspondence article was published by The Lancet from the University of Erlangen–Nuremberg in Germany in collaboration with the Bavarian Cancer Research Center (BZKF). This article discusses the CAR T cell therapy that rescued an adolescent with rapidly progressive Systemic Lupus Erythematosus nephritis from hemodialysis. The female patient was 15 years old, and despite escalating treatment regimens, including hydroxychloroquine, azathioprine, mycophenolate mofetil, and B-cell-targeting antibody belimumab, her kidney function deteriorated 6 months after disease onset. The patient developed severe nephritis with proteinuria and microscopic hematuria and all those diagnostic signs consistent with class 4 lupus nephritis. Additional signs of systemic lupus erythematosus included rash, fever, and arthritis. Due to the rapidly progressing renal dysfunction, a high-dose methylprednisolone and cyclophosphamide regimen and plasma separation was initiated, which led to a decrease in autoantibody levels. However, the treatment was not able to prevent renal dysfunction, resulting in the patient requiring treatment for hemodialysis and hypertension.
CD19-targeting CAR T cell therapy was then initiated following transfection of isolated T cells with the lentiviral vector Miltenyi Biotec, Bergisch Gladbach, Germany encoding a second-generation 4-1BB-based CD19 CAR using the CliniMACS Prodigy system (CliniMACS Prodigy, Bergisch Gladbach, Germany). Therefore, in this paediatric patient with systemic lupus erythematosus, the first known to be treated with anti-CD19 CAR T cells, therapy achieved sustained remission in a rapidly progressive and refractory lupus nephritis. Contrary to the previously reported results in adults with systemic lupus erythematosus receiving anti-CD19 CAR T-cell therapy, this patient had end-stage renal disease, requiring haemodialysis every 2–3 days. Despite kidney failure, CAR T-cell therapy was safe and well tolerated due to appropriate dose adjustment of lymphodepletion. As demonstrated in this article, anti-CD19 CAR T-cell therapy can rescue a patient with lupus nephritis from haemodialysis and long-term dependency on medications that might substantially reduce health-related consequences and economic burden. The patient, who had early onset and rapidly progressive lupus nephritis, illustrates that early intervention is crucial, in particular in juvenile-onset patients who frequently have an aggressive course of systemic lupus erythematosus and can develop disease-related organ damage within the first 2 years. The long-term efficacy and safety of CD19-targeted CAR T-cell therapy in paediatric patients with autoimmune diseases have yet to be confirmed and systematically evaluated in clinical studies. This case strongly supports the early access of this new therapeutic option in clinical trials for paediatric patients with systemic lupus erythematosus.