Daratumumab monotherapy for refractory lupus nephritis

Abstract

Abstract Refractory lupus nephritis (RLN) is a clinical condition with high risk of a poor outcome and often life-threatening. Six patients (one male and 5 females), aged 41.3 years (range 20 to 61 years) were treated with Daratumumab monotherapy, a monoclonal antibody targeting CD38 which is highly expressed on the surface of many immune cells, especially plasma cells. The treatment protocol consisted of 16 mg/kg daratumumab administered intravenously weekly for 8 weeks, then every two weeks 8 more times, and lastly monthly (maximum 8 infusions). All patients failed previous treatments with the Standard of Care (SOC) including mycophenolate mofetil (MMF), cyclophosphamide (CYC), azathioprine and rescue therapies including Rituximab (RTX), Ocrelizumab, Belimumab, and iv IgG. One out of six patients did not show clinical response after 6 months of therapy, and Daratumumab was discontinued. Five patients showing a clinical response over the same period continued to be treated and reached a 12-month observation. Renal biopsy performed before daratumumab administration revealed a class IV LN in 1 patient, class V LN in 1 patient, class III + V LN in 1 patient and class IV + V LN in the other 2. Three patients achieved a complete renal response and the other two a partial renal response. A significant decrease in proteinuria from 5.6 gr/24 hours to 0.8 g/24 hours (p = 0.001) was achieved at 12 months. The mean value of serum Creatinine (sCr) decreased from 2.3 to 1.5 mg/dl. Improvement of clinical symptoms was paralleled by seroconversion of anti-double-stranded DNA antibodies (p = 0.03), significant decrease in interferon-gamma values (p = 0.0006), BMCA-B-cell maturation antigen (p = 0.0005) and soluble CD163 levels (p = 0.045), and increase in C4 (p = 0.018) and IL 10 levels (p = 0.0006). Clinical remission was substantiated by improvement of SLEDAI-2K score (p = 0.03). Daratumumab was generally well tolerated. These data suggest that Daratumumab administered alone (i.e., without any other immunosuppressant or agents targeting B-cell activating factor) is highly effective in RLN.