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.

Fig. 1. Laboratory profiles.

Trend of proteinuria, sCr, C3 and C4 in responder patients at baseline and at 3 months, 6 months and 12 months. n = 5 biologically independent samples were used for each determination (one per patient/timepoint). Box plots show median and 1st–3rd interquartile range; whiskers indicate minimum–maximum. P ≤ 0.05 was considered significant. uPt, proteinuria.

Fig. 2. Serum concentrations of the INF-γ (shown as median and interquartile range), IL-10, sBCMA and sCD163 and scatter dot plots with results shown as median and range.

*P < 0.05. TO, baseline; T6, 6 months; T12, 12 months. n = 5 biologically independent samples were used for each determination (one per patient/timepoint). The Wilcoxon matched‐pairs signed‐rank test was applied to investigate variations in parameters after treatment. P ≤ 0.05 was considered significant.

Fig. 3. Immunological profiles.

a–d, Top panels: Associations of serum. IFN-γ (pg ml⁻¹) (a), sBCMA (ng ml⁻¹) (b), sCD163 (pg ml⁻¹) (c), IL-10 (pg ml⁻¹) (d), and disease activity in SLE patients. Cytochines levels are expressed in ng ml⁻¹. Rs: Spearman’s correlation coefficient, SLEDAI-2K: Systemic Lupus Erythematosus Disease Activity 2000 Index. Middle panel: Correlation matrix heat map of sBCMA and the cytokines IFN-γ, sCD163 and IL-10. Bottom panel: Serum levels of anti-dsDNA (scatter dot plots with results shown as median and range). T0, baseline; T3, 3 months; T6, 6 months; T12, 12 months. The Spearman rank correlation coefficient (rs) was used to assess correlations between parameters. P ≤ 0.05 was considered significant.