Rheumatology (Oxford, England) · 2026
Anti-CD19 CAR-T cell therapy as rescue treatment in systemic sclerosis relapsing after autologous haematopoietic stem cell transplantation: a case series.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rimar Doron, David Paula, Jacoby Elad, Shapira-Frommer Ronnie, Itzhaki Orit, Keret Shiri, Slobodin Gleb, Marcus Ronit, Shimoni Avichai, Yerushalmi Ronit, Danylesko Ivetta, Tov Noga Shem, Avigdor Abraham, Lidar Merav
Аннотация
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.
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.