Anti CD19 targeting CAR T cell therapy in ANCA-associated vasculitis

OBJECTIVES: To present a successful case study of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a patient with relapsing granulomatosis with polyangiitis (GPA). METHODS: A 69-year-old male patient suffering from relapsing GPA refractory to standardized immunosuppression underwent an experimental therapy involving CD19-targeting CAR T cells. The conditioning regimen consisted of fludarabine and cyclophosphamide. Follow-up intervals scheduled at 1 to 3 months' intervals, incorporated evaluations of the BVAS, CT scans of the lungs, CRP, peripheral white blood cell count (WBC), lactate dehydrogenase, ANCA, immunoglobulin levels, post-CAR T-cell treatment surveillance including (CAR)-lymphocyte counts. RESULTS: The patient was diagnosed with GPA involving the lungs in 2019. He showed a relapsed refractory disease course in spite of treatment with rituximab, cyclophosphamide, avacopan, azathioprine, leflunomide and prednisolone. At presentation for CAR T-cell treatment, the BVAS was 14, inflammation markers were elevated, and pulmonary infiltrates were visible on the CT scan. CAR T-cell therapy was well-tolerated with no cytokine release syndrome (CRS) or neurotoxicity, and led to rapid improvement of clinical condition, as well as radiological and laboratory test results. CAR T cells expanded with a transient peak but were not anymore detectable in the peripheral blood around day 90. In line the significant B-cell depletion and hypogammaglobulinemia observed post-treatment showed gradual recovery. At the latest follow-up of 12-months post-treatment, the patient is in complete remission without further medication. CONCLUSION: CD19-targeted CAR T-cell therapy was safe and efficacious in a patient with relapsed and refractory GPA. CAR T-cell therapy has the potential to transform disease management and improve long-term outcomes for affected patients.