Anti-CD19 CAR-T cell therapy as rescue treatment in systemic sclerosis relapsing after autologous haematopoietic stem cell transplantation: a case series.

Abstract

Autologous haematopoietic stem cell transplantation (AHSCT) is an established therapy for diffuse progressive systemic sclerosis (DpSSc), improving progression-free and overall survival compared with cyclophosphamide; however, relapse occurs in ∼12-17% of patients. Chimeric antigen receptor T cell (CAR-T) therapy offers a novel approach to deplete autoreactive B cells. This study aimed to assess the feasibility, efficacy and safety of anti-CD19 CAR-T therapy as a rescue treatment in patients with SSc relapse following AHSCT. Thirty SSc patients underwent AHSCT at our centre over the past decade. Relapse was defined as an increase in modified Rodnan skin score (mRSS) ≥25% or a decrease in forced vital capacity (FVC) ≥10%. Three female patients (mean age 50 ± 13 years) relapsed after a mean of 2.8 ± 3.6 years. They received autologous FMC63-28-CD3ζ CAR-T cells (0.6 × 106/kg) following lymphodepletion with fludarabine (75 mg/m2 total) and cyclophosphamide (900 mg/m2). Clinical, functional and quantitative CT outcomes were assessed over 12 months. Two patients had a favourable clinical response with FVC improvement (≥10%) and ≥25% reduction in mRSS, accompanied by reduced ground-glass opacities on CT. One patient showed no CAR-T expansion and accordingly no clinical response. Adverse events were mild, limited to grade 1 cytokine release syndrome and one line-related thrombosis, without long-term haematological toxicity. Anti-CD19 CAR-T therapy was well tolerated and associated with clinical and radiological improvement in SSc patients relapsing after AHSCT. However, the absence of CAR-T expansion in one patient raises concerns regarding feasibility and warrants further mechanistic investigation.