Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus

Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.) Long-lived plasma cells that express CD38 are thought to play a pathogenic role in systemic lupus erythematosus. The anti-CD38 antibody daratumumab was used to treat two patients with treatment-refractory, life-threatening lupus complications, and both had significant clinical improvement.