Autologous CD19- targeting CAR T cells in refractory juvenile dermatomyositis.

OBJECTIVES: To report safety and efficacy of CD19-targeting CAR T cells in a child with refractory juvenile dermatomyositis (JDM).

PATIENTS AND METHODS: We describe the case of a 12-year-old Caucasian boy with severe, chronically active JDM, refractory to multiple immunosuppressive treatment lines, including B-cell depletion with rituximab. The patient received a single infusion of fresh, autologous, second-generation anti-CD19 CAR T-cell product (lentiviral vector) manufactured on the Prodigy device (1x106 CAR T cells/kg), after lymphodepletion with cyclophosphamide (1000 mg/m2 over 2 days) and fludarabine (90 mg/m2 over 3 days). Immunosuppressive and glucocorticoid treatment were withdrawn before leukapheresis and CAR T-cell infusion.

RESULTS: Before anti-CD19 CAR T-cell therapy, the patient had persistent severe skin and muscular disease activity. CAR T cells expanded significantly (peak at day 7, 32.69 cells/μL). Complete B-cell depletion was documented on day 5 in blood and at week 2 in bone marrow. The patient presented fever as part of mild cytokine release syndrome (G1), transient anemia (G2) and neutropenia (G4). Neither infection nor neurotoxicity were observed. Laboratory tests, MRI imaging, Physician's Global Assessment of disease activity (PGA), Childhood Myositis Assessment Scale (CMAS) and Cutaneous Assessment Tool for myositis (CAT) were performed at baseline and follow-up to assess treatment response, showing remarkable progressive improvement that persists over time, even after B-cell recovery.

CONCLUSIONS: This JDM patient with severe chronic disease, refractory to multiple treatments, achieved sustained B-cell depletion and ongoing immunosuppressive drug-free clinical and radiological improvement eight months after a single infusion of anti-CD19 CAR T cells.