Objective To report the first case of a patient with refractory childhood-onset SLE successfully treated with anti-CD19 CAR-T cell therapy.

Methods A single infusion of fresh, autologous second-generation anti-CD19 CAR-T product (lentivirus) manufactured on the Prodigy device was administered (1x10⁶ CAR-T cells/kg).

Results A female patient with one-year history of childhood-onset SLE presented at our attention at the age of 15 years with persistent clinical (hemolytic anemia, thrombocytopenia, malar rash, class II/V lupus nephritis, interstitial lung disease, pulmonary hypertension (PAH) and pericardial effusion) and serological (hypocomplementemia and high ANA and anti-dsDNA antibodies) active disease. She received multiple treatments, including high-dose glucocorticoids (GC), hydroxychloroquine, mycophenolate (MMF), rituximab and IV cyclophosphamide (CYC) without reaching remission. She was started on sildenafil and bosentan for PAH. She developed osteoporosis and hypertension secondary to GC therapy, and 2 severe systemic infections, requiring prolonged hospitalization. Anti-CD19 CAR-T cell therapy was considered and performed after lymphodepletion with CYC (1500mg/m2) and fludarabine (90mg/m2). Immunosuppressants (GC, MMF and hydroxychloroquine) were withdrawn before CAR-T therapy. After the CAR-T cell infusion, the patient presented fever, rash and pleural effusion as part of mild cytokine release syndrome (G1) and transient anemia (G2) and neutropenia (G3). No infection or neurotoxicity were observed. The CAR-T cells expanded significantly (peak at day 12, 52 cells/uL). Circulating B cells at baseline were 111 cells/uL. Complete blood B-cell depletion was achieved on day 7. Bone marrow aspirates at week 2 and 4 showed complete B-cell depletion. Urinalysis normalized at week 3. Complement levels normalized at week 6. ANA and anti-dsDNA titers significantly decreased (from 1:5120 and 1:1280 at baseline to 1:640 and 1:160 at week 8, respectively). A normal right ventricular systolic pressure and NT-ProBNP levels were found at week 2 and 6, allowing bosentan discontinuation. At time of CAR-T infusion, the SLEDAI-2K score was 22, which rapidly improved reaching a score of 2 at week 6 and 10. Patient was on persistent drug-free remission at last follow-up (week 10).

Conclusions In this SLE patient with severe refractory disease, B-cell depletion and drug-free remission were rapidly achieved after anti-CD19 CAR-T cells infusion. Long-term efficacy assessment is needed.