BCMA-targeted CAR T cell therapy can effectively induce disease remission in refractory lupus nephritis

OBJECTIVES: This study aims to evaluate the safety and efficacy of anti-B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells in treating refractory lupus nephritis (LN). METHODS: This is an open-label, single-arm clinical trial assessing anti-BCMA CAR T cells in treating refractory LN patients. CAR T cells were infused following lymphodepletion therapy with cyclophosphamide and fludarabine. Patients were regularly followed up, in which clinical assessments were performed and laboratory indices were collected. Repeated renal biopsies and single cell RNA sequencing in certain patients were performed to help evaluate the therapeutic efficacy. The primary endpoints were the safe dosage of single infusion and the occurrence of adverse events, while the secondary endpoints focused on the therapeutic efficacy (eg, changes of Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2000]). RESULTS: Seven biopsy-confirmed LN patients were enrolled in this study with a median follow-up of 9 months, whose peripheral B cells were effectively eliminated within the first month postinfusions and restored within 3 months except one patient. Hypogammaglobulinemia was frequently observed in this study. Only one case of grade 1 cytokine release syndrome was noted, and no immune effector cell-associated neurotoxicity syndrome or severe infection was reported. SLEDAI-2K scores decreased from a median of 18 (range 10-22) at baseline to 0 (range 0-4) at the last follow-up, and 5 out of 7 patients achieved definition of remission in systemic lupus erythematosus (DORIS) complete remission. Decreased deposition of immune complex, reduced clonal abundance, and alleviated proinflammatory status of peripheral lymphocytes were also observed in repeated renal biopsy and transcriptomic analyses,. CONCLUSIONS: Anti-BCMA CAR T therapy can help LN patients inducing and maintaining disease remission status safely and effectively, which indicated the potential feasibility of the BCMA-only-targeting strategy in treating autoimmune diseases with abnormal humoral immune responses through CAR products.