CAR T-cell therapy rescues adolescent with rapidly progressive lupus nephritis from haemodialysis

• Published in: The Lancet (British edition) 2024-04, Vol.403 (10437), p.1627-1630
• Main Authors: Krickau, Tobias, Naumann-Bartsch, Nora, Aigner, Michael, Kharboutli, Soraya, Kretschmann, Sascha, Spoerl, Silvia, Vasova, Ingrid, Völkl, Simon, Woelfle, Joachim, Mackensen, Andreas, Schett, Georg, Metzler, Markus, Müller, Fabian
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Adoptive transfer; Adults; Anti-DNA antibodies; Antibodies; Antihypertensives; Arthritis; Autoantibodies; Autoimmune diseases; CD19 antigen; Cell therapy; Chimeric antigen receptors; Chronic conditions; Creatinine; Cyclophosphamide; Cytokine storm; Depletion; Disease Progression; Drug dosages; End-stage renal disease; Female; Hematuria; Hemodialysis; Histones; Humans; Hypertension; Immunosuppressive agents; Immunotherapy, Adoptive - methods; Kidney diseases; Lupus; Lupus nephritis; Lupus Nephritis - therapy; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Methylprednisolone; Morbidity; Nephritis; Patients; Pediatrics; Quality of life; Receptors, Chimeric Antigen; Remission; Remission (Medicine); Renal Dialysis; Renal failure; Renal function; Systemic lupus erythematosus; Therapy
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(24)00424-0

Morbidity and mortality in juvenile-onset systemic lupus erythematosus are higher than adult-onset disease, and children with lupus nephritis have higher scores on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).2,3 End-stage renal disease and permanent haemodialysis are severe adverse events than can occur due to juvenile-onset and adult-onset systemic lupus erythematosus, with 15% of all patients with lupus nephritis developing end-stage renal disease.4 The therapeutic goal of complete remission of lupus nephritis is only reached in 60% of patients by conventional therapies, including immunosuppressive drugs and B-cell-depleting antibodies,3 and two-thirds of adults with juvenile-onset systemic lupus erythematosus develop organ damage and impaired health-related quality of life without reaching drug-free remission.5 Due to their high B-cell depletion activity, CD19-targeted chimeric antigen receptor (CAR) T cells are a potentially powerful strategy to treat autoimmune diseases, such as systemic lupus erythematosus.6,7 In a small case series of eight patients aged 18–38 years with treatment-refractory systemic lupus erythematosus, adoptive transfer of CD19-targeted CAR T cells induced a deep reset of B cells leading to abrogation of autoreactive antibodies and durable remission, including abrogation of lupus nephritis with a follow-up time of 6–29 months.8 Herein, we report on a 15-year-old female patient with severe and rapidly progressive systemic lupus erythematosus. Low levels of complement and presence of several autoantibodies including anti-nuclear-antibody anti-double-stranded DNA (anti-dsDNA; 4545 IU/mL [normal range is