EFFICACY OF ANTI-CD38 TREATMENT WITH DARATUMUMAB IN TWO CASES OF REFRACTORY AND SEVERE SJÖGREN DISEASE
Authors: Gaetane Nocturne et al.
In 10% of Sjögren’s patients, severe and potentially life-threatening systemic disease may occur. Plasmablasts and plasma cells are key drivers of disease activity. Daratumumab, a monoclonal antibody targeting CD38 and approved for multiple myeloma, depletes plasmablasts and plasma cells.
Two patients with severe Sjögren’s refractory to rituximab (RTX) were successfully treated with daratumumab. Patient 1 is a 18-year-old woman who had hypergammaglobulinemia (18 g/l) and severe hypertriglyceridemia (52 g/l) due to anti GPIHBP1 antibodies. Patient 2 is a 68-year-old woman with type II cryoglobulinemia, vasculitis, polyneuropathy, and glomerulonephritis. After 8 months of follow-up, patient 1 showed normalized triglyceride levels and gammaglobulin levels, and a dramatic decrease in anti-GPIHBP1 antibodies from 6121 U/ml to 234 U/ml. Patient 2 was in clinical and ‘laboratory’ remission. There were no severe adverse events.
Similar to two phase 2 studies with inhibitors of B-cell activation also presented at this ACR (iscalimab, a mAb directed against CD40 and dazodalibep, a CD40L antagonist), daratumumab may be an effective and readily available drug in severe and refractory Sjögren’s syndrome, particularly when systemic manifestations are driven by pathogenic autoantibodies. Further studies are needed.