Rheumatology (Oxford, England) · 2026
CAR-T as a salvage treatment in polyrefractory RA.
СтатьяНазвание и аннотация: Перевод в очереди
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Lidar Merav, David Paula, Jacoby Elad, Shapira-Frommer Ronnie, Itzhaki Orit, Eshet Yael, Eshed Iris, Marcus Ronit, Shimoni Avichai, Yerushalmi Ronit, Danylesko Ivetta, Tov Noga Shem, Slobodin Gleb, Kaly Lisa, Samara Reem, Avigdor Abraham, Rimar Doron
Аннотация
OBJECTIVES: To evaluate the utility of CD19-directed chimeric antigen receptor T cell (CAR-T) therapy in patients with persistent inflammatory refractory RA (PIRRA), who failed ≥5 biologic/targeted synthetic DMARDs classes.
METHODS: Three women with long-standing, seropositive PIRRA received autologous anti-CD19 CAR-T therapy with CD 28 co-stimulation. After lymphodepletion with fludarabine and cyclophosphamide, an infusion of 0.6-1 × 106 CAR-T cells/kg was administered. Clinical, laboratory, imaging and histological outcomes were assessed up to 18 months.
RESULTS: Median age was 54 years (range 39-68), and median disease duration was 14 ± 3.1 years. All developed grade 3 cytokine release syndrome (CRS), and one developed grade 4 ICANS. No long-term toxicities were observed, except for hypogammaglobulinemia, that has not required replacement therapy. Within 3 months, two patients achieved remission, and one had low disease activity. At the last follow-up, two remained in drug-free remission, and one attained low disease activity with abatacept and MTX. HAQ-DI scores improved from severe disability to near-normal. RF and ACPA titres markedly declined. Furthermore, imaging demonstrated resolution of synovitis and clearance of CD19+B cells from the synovium establishing histological remission.
CONCLUSION: CD19 CAR-T therapy induced profound, durable responses in extremely severe patients with seropositive PIRRA. Despite significant acute toxicities, recovery was complete and long-term safety was favourable. These findings suggest that CAR-T may provide a transformative benefit in severe RA, warranting controlled clinical trials.
METHODS: Three women with long-standing, seropositive PIRRA received autologous anti-CD19 CAR-T therapy with CD 28 co-stimulation. After lymphodepletion with fludarabine and cyclophosphamide, an infusion of 0.6-1 × 106 CAR-T cells/kg was administered. Clinical, laboratory, imaging and histological outcomes were assessed up to 18 months.
RESULTS: Median age was 54 years (range 39-68), and median disease duration was 14 ± 3.1 years. All developed grade 3 cytokine release syndrome (CRS), and one developed grade 4 ICANS. No long-term toxicities were observed, except for hypogammaglobulinemia, that has not required replacement therapy. Within 3 months, two patients achieved remission, and one had low disease activity. At the last follow-up, two remained in drug-free remission, and one attained low disease activity with abatacept and MTX. HAQ-DI scores improved from severe disability to near-normal. RF and ACPA titres markedly declined. Furthermore, imaging demonstrated resolution of synovitis and clearance of CD19+B cells from the synovium establishing histological remission.
CONCLUSION: CD19 CAR-T therapy induced profound, durable responses in extremely severe patients with seropositive PIRRA. Despite significant acute toxicities, recovery was complete and long-term safety was favourable. These findings suggest that CAR-T may provide a transformative benefit in severe RA, warranting controlled clinical trials.