Heterogeneous responses of IM19 anti-CD19 CAR T-cell therapy in refractory systemic lupus erythematosus: an open-label pilot study and a mini-review.

Abstract

This study aims to evaluate the efficacy and safety of IM19, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell, in patients with refractory systemic lupus erythematosus (SLE), with a particular focus on lupus nephritis (LN). This is an open-label, single-arm clinical trial. IM19 was administered following lymphodepletion. Repeated renal biopsies were performed at day 180. Single-cell RNA sequencing on peripheral blood mononuclear cells was performed pre- and 180-day post-CAR-T infusion. A literature search on the efficacy of CAR T-cell therapy in LN in PubMed database was conducted. Six patients with refractory SLE and renal involvement were enrolled. IM19 therapy was well tolerant, with mild cytokine release syndrome occurring in 4 patients. The median Systemic Lupus Erythematosus Disease Activity Index-2000 score decreased from 12 (range, 10-24) to 4 (range, 2-8) at day 90, and remained stable at 5 (range, 2-6) at day 180. The renal responses were heterogeneous with 2 complete responders, 2 partial responders, and 2 nonresponders. Repeated renal biopsies showed no B-cell infiltration, but dominant chronic changes and podocytopathies post-CAR-T therapy. A mini-review demonstrated that the renal complete response rate of CAR-T therapy was 72.4%, and advanced age was associated with suboptimal response. Single-cell analysis confirmed B-cell reconstitution in 3/6 patients. IM19 CAR T-cell therapy demonstrated a favourable safety profile and clinically meaningful systemic improvement. Responses to CAR-T therapy in LN were variable. Chronic renal manifestations, podocytopathy, and ageing were associated with suboptimal therapeutic outcome.