Safety and Efficacy of CD19 Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) in the Treatment of Refractory Membranous Nephropathy
This study is a single-center, prospective, exploratory Phase I clinical trial initiated by the team led by Associate Professor He Lijie from the Department of Nephrology, Xijing Hospital. Prior to receiving CAR-T cell therapy, patients will undergo lymphodepletion chemotherapy with cyclophosphamide (fludarabine will be added if necessary). After prophylactic administration of antihistamines and acetaminophen, patients will be infused with CD19 CAR-T cells at a dose of 1×10⁶ cells/kg. In the subsequent 2 weeks, patients will be hospitalized for monitoring of vital signs and adverse reactions. The planned follow-up duration of this study is 1 years.
• Confirmed as primary membranous nephropathy (PMN) by renal biopsy.
• Classified as moderate-risk or high-risk refractory membranous nephropathy (rMN).
• Moderate-risk rMN is defined as: eGFR ≥ 90 ml/min/1.73m² AND 24-hour urinary protein \> 3.5g/d, with a reduction of no more than 50% within 6 months of receiving renin-angiotensin system inhibitor (RASi) therapy.
• High-risk rMN is defined as meeting one of the following:
‣ eGFR \< 60 ml/min/1.73m² and/or persistent proteinuria \> 8g/d for more than 6 months.
⁃ Normal eGFR with proteinuria \> 3.5g/d and ≤50% reduction after 6 months of RASi therapy, PLUS at least one of the following: Serum albumin \< 25g/L; PLA2R antibody \> 50 RU/mL; Urinary α1-microglobulin \> 40 μg/min; Urinary IgG \> 1 μg/min; Urinary β2-microglobulin \> 250 mg/d; IgG/albumin clearance ratio \> 0.20.
• Diagnosis of rMN requires failure of adequate first-line immunosuppressive therapy (≥6 months of steroids+cyclophosphamide, CNI, or rituximab), defined by any of the following: persistent high-titer anti-PLA2R antibody; for antibody-negative patients, persistent nephrotic syndrome (protein \>3.5g/d, albumin \<30g/L); \<50% reduction in proteinuria.
• Age ≥ 18 years.
• Adequate organ function, defined as:
‣ Renal: eGFR ≥ 30 ml/min/1.73m².
⁃ Hepatic: ALT and AST ≤ 2.5 x ULN; Total bilirubin ≤ 1.5 x ULN.
⁃ Cardiac: LVEF ≥ 50%; NYHA Class I or II; No significant arrhythmias requiring intervention; No major cardiovascular events within the past 6 months.
⁃ Respiratory: SpO2 \> 92% on room air.
• Ability to understand and willingness to sign an Informed Consent Form.