Daratumumab monotherapy for refractory lupus nephritis

Abstract

Treatment-refractory lupus nephritis (LN) has a high risk of a poor outcome and is often life-threatening. Here we report a case series of six patients (one male and five females) with a median age of 41.3 years (range, 20–61 years) with refractory LN who received renal biopsies and were subsequently treated with intravenous daratumumab, an anti-CD38 monoclonal antibody (weekly for 8 weeks, followed by eight biweekly infusions and up to eight monthly infusions). One patient did not show any improvement after 6 months of therapy, and daratumumab was discontinued. In five patients, the mean disease activity, as assessed by the Systemic Lupus Erythematosus Disease Activity 2000 index, decreased from 10.8 before treatment to 3.6 at 12 months after treatment. Mean proteinuria (5.6 g per 24 h to 0.8 g per 24 h) and mean serum creatinine (2.3 mg dl−1 to 1.5 mg dl−1) also decreased after 12 months. Improvement of clinical symptoms was accompanied by seroconversion of anti-double-stranded DNA antibodies; decreases in median interferon-gamma levels, B cell maturation antigen and soluble CD163 levels; and increases in C4 and interleukin-10 levels. These data suggest that daratumumab monotherapy warrants further exploration as a potential treatment for refractory LN.

CD38 als innovatives therapeutisches Target zur Plasmazelldepletion bei Autoimmunerkrankungen

“…Bei 5 von 6 Patienten konnte eine komplette renale Remission erzielt werden. Trotz Abfall der IgG-Spiegel im Serum von 50 % nach 6 Monaten wurden keine schwerwiegenden unerwünschten Ereignisse beobachtet 12 .…”

Autoimmune Diseases and Plasma Cells Dyscrasias: Pathogenetic, Molecular and Prognostic Correlations

“…Indeed, a considerable (about 60%) decrease in pathogenic anti-dsDNA antibodies was related to daratumumab. Improvements in many clinical characteristics, including pericarditis, autoimmune hemolytic anemia, lupus nephritis and mucocutaneous symptoms in SLE patients, were attributed to the use of daratumumab [ 124 ].…”

Lupus Nephritis Risk Factors and Biomarkers: An Update

“…To this end, the European Medicines Agency (EMA) allows three add-on therapies targeting the type I IFN receptor (anifrolumab), the ISG BAFF/BLyS (belimumab), or the non-nephrotic calcineurin inhibitor voclosporin. Ongoing trials further support in refractory SLE/LN to target the type I/I IFN JAK/STAT pathway (e.g., tofacitinib), to deplete tissular B cells ± plasmocytes (CAR T cells and obinituzimab instead of rituximab), or to deplete CD38-positive plasmocytes (daratumab) [130].…”