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Objectives To provide updated long-term safety and efficacy of ICG318 to treat refractory systemic lupus erythematosus (SLE) and lupus nephritis (LN) in a phase I clinical trial. We report up to 67-month follow-up.Methods Twelve patients (P) with refractory SLE, including 10 with biopsy-confirmed LN, were enrolled. P3-13 (excluding P11) received 3×10^6 autologous ICG318 cells/kg following non-fludarabine conditioning with single-agent cyclophosphamide (0.3 g/m2). Efficacy was assessed by stringent SLE CR criteria (sCR) requiring medication-free DORIS remission, complete renal response (CRR) and complete serological absence of disease. Endpoints included safety, serologies, medication use, B cell counts, immunoglobulin (IgG, IgM, IgA) and complement levels, and long-term clinical outcomes. Nine patients had follow-up renal biopsies.Results The median follow-up was 30 months (range, 19 to 67). Ten of 12 patients achieved enduring, sCR with no severe adverse events, infections attributed to ICG318, immune effector cell associated neurotoxicity syndrome, or cytokine release syndrome (CRS) above grade 1. All CRS events resolved with supportive care. Throughout follow-up, normalization of humoral cell counts, immunoglobulin and complement levels, and absence of all 9 autoantibodies examined was sustained in all patients, except P13. Eleven of 12 patients remained in durable DORIS remission with mean SLEDAI-2K scores decreasing from 9.5 at baseline to approximately 0.67 at the last follow-up. CRR was achieved in 9/10 LN patients. Repeat renal biopsies showed marked improvement with reductions in active inflammatory lesions in all 9 patients. P9 had 2 successful pregnancies post-ICG318, suggesting the therapy does not compromise female fertility.Conclusions In this landmark long-term follow-up, ICG318 exhibited remarkable safety and efficacy achieving durable sCR in 10 of 12 patients and reconstituted humoral immunity in all patients. Despite serological absence of disease, P6 failed to satisfy DORIS remission and CRR criteria due to persistent proteinuria from chronic, not active, renal disease evidenced by no IgG complexes on biopsy. Thus, 11 of 12 patients achieved medication-free serological remission. These findings support targeting both CD19 and BCMA in SLE/LN to achieve long-term sCR. With P1 sCR approaching 6 years, this may offer a first glimpse into the curative potential of CAR T-cell therapy in autoimmune diseases.