Abstract Body

Refractory lupus nephritis (RLN) can be defined as failure to attain clinical remission after appropriate induction immunosuppressive therapy. RLN is associated with an increased risk of progression to end-stage kidney disease and mortality. There are no robust guidelines for treating RLN. However, the majority of new agents proposed for systemic lupus erythematosus (SLE) have been tested mainly in RLN patients. Apart from autologous hematopoietic stem cell transplantation, novel approaches include proteasome inhibitors (i.e., Bortezomib), new calcineurin inhibitors (i.e., Voclosporin), B cell modulating therapies (i.e., Belimumab), and B cell depleting agents (i.e., Rituximab and Obinotuzumab). Obinotuzumab, tested in a randomized controlled trial, was found to enhance the number of overall renal response when added to standard of care (SOC) consisting of a mycophenolate mofetil (MMF)-based regimen. In a recently published case control study, as compared to SOC (both MMF-based and cyclophosphamide-based regimens), Rituximab (RTX) administered in the context of an intensive B cell depletion protocol (4 plus 2 infusions of 375 mg/sm) together with low doses CYC, was found to significantly reduce the probability of relapse even in the absence of immunosuppressive maintenance therapy. Finally, a recently emerged agent is the anti-CD38 monoclonal antibody, Daratumumab. CD38, also known as cyclic ADP ribose hydrolase, is a glycoprotein found on the surface of many immune cells. It also functions in cell adhesion, signal transduction, and calcium signaling. A cell type-specific dysregulation of CD38 expression has been observed in patients with SLE. CD38 is highly expressed on plasma cells (PC), and Daratumumab has been shown to cause a depletion of highly expressing CD38 PC in the bone marrow. Two patients with refractory SLE have been recently reported to be successfully treated with Daratumumab combined with Bortezomib. Our group treated six RLN patients with Daratumumab alone. They include 2 males and 4 females, mean age 37.5 yrs (20-60) who had previously received SOC (MMF, CYC, azathioprine) plus rescue therapies (including RTX, Ocrelizumab, Belimumab, and ivIG). Renal biopsy, performed before starting Daratumumab, showed class IV or class II+V LN. Following Daratumumab the patients showed a significant reduction of serum creatinine and proteinuria with disappearance of anti-DNA antibodies. Daratumumab seems to be a new excellent candidate for the rescue treatment of Refractory Lupus Nephritis.