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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.