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May 2025
Journal Article
Title
Effective use of anti-CD19 chimeric antigen receptor T cells in a case of treatment-resistant granulomatosis with polyangiitis
Abstract
BACKGROUND:
Granulomatosis with polyangiitis (GPA), the most common form of antineutrophil cytoplasmic antibody (ANCA)–associated small vessel vasculitis (AAV), can cause life-threatening organ damage, and its treatment, consisting of immunosuppressive therapy, is associated with serious side effects. Rituximab, an anti-CD20 monoclonal antibody, is considered the standard treatment for AAV; however, its effectiveness may be limited because autoantibody-producing plasmablasts and plasma cells are not targeted and tissue depletion is not profound. In rituximab-refractory cases, deep tissue depletion of B cells using anti-CD19 chimeric antigen receptor (CAR) T-cell therapy could provide an effective alternative. CAR T cells have already been successfully used in patients with treatment-refractory autoimmune diseases, and 1 patient with AAV has recently been reported.
CASE REPORT:
A 40-year-old male patient was diagnosed with GPA in April 2023, fulfilling 2022 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria and having histologically proven small vessel vasculitis. Between April and December 2023, the patient received 7 rituximab infusions (cumulative dose, 5790 mg), 5 cyclophosphamide infusions (cumulative dose, 4200 mg), cyclosporin A, avacopan, and frequent prednisolone escalations (Fig, A). While C-reactive protein (CRP) and proteinase 3 (PR3)–ANCA levels showed partial normalization after 1 year of therapy, severe pulmonary inflammatory lesions persisted, requiring daily prednisolone (≥10 mg) to prevent relapses. Imaging studies revealed unresolved lung nodules and a cavitary lesion in the left lower lobe (Fig, B, top). Additionally, [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) demonstrated heightened glucose metabolism in the lungs, indicative of ongoing disease activity (Fig, C, top).
Granulomatosis with polyangiitis (GPA), the most common form of antineutrophil cytoplasmic antibody (ANCA)–associated small vessel vasculitis (AAV), can cause life-threatening organ damage, and its treatment, consisting of immunosuppressive therapy, is associated with serious side effects. Rituximab, an anti-CD20 monoclonal antibody, is considered the standard treatment for AAV; however, its effectiveness may be limited because autoantibody-producing plasmablasts and plasma cells are not targeted and tissue depletion is not profound. In rituximab-refractory cases, deep tissue depletion of B cells using anti-CD19 chimeric antigen receptor (CAR) T-cell therapy could provide an effective alternative. CAR T cells have already been successfully used in patients with treatment-refractory autoimmune diseases, and 1 patient with AAV has recently been reported.
CASE REPORT:
A 40-year-old male patient was diagnosed with GPA in April 2023, fulfilling 2022 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria and having histologically proven small vessel vasculitis. Between April and December 2023, the patient received 7 rituximab infusions (cumulative dose, 5790 mg), 5 cyclophosphamide infusions (cumulative dose, 4200 mg), cyclosporin A, avacopan, and frequent prednisolone escalations (Fig, A). While C-reactive protein (CRP) and proteinase 3 (PR3)–ANCA levels showed partial normalization after 1 year of therapy, severe pulmonary inflammatory lesions persisted, requiring daily prednisolone (≥10 mg) to prevent relapses. Imaging studies revealed unresolved lung nodules and a cavitary lesion in the left lower lobe (Fig, B, top). Additionally, [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) demonstrated heightened glucose metabolism in the lungs, indicative of ongoing disease activity (Fig, C, top).
Author(s)