# Daratumumab in systemic lupus erythematosus: a single-arm phase 2 trial

## TL;DR

This study shows that daratumumab, a drug targeting antibody-producing cells, significantly improves symptoms and immune markers in lupus patients.

## Contribution

Demonstrates the efficacy of daratumumab in reducing disease activity and modulating immune responses in systemic lupus erythematosus.

## Key findings

- Daratumumab reduced anti-dsDNA antibody levels by a median of 109.6 IU/ml at week 12.
- All patients showed a 100% SRI-4 response rate, indicating clinical improvement.
- Treatment depleted ASCs, reduced interferon activity, and modulated T-cell responses.

## Abstract

Antibody-secreting cells (ASCs) play a central role in the pathophysiology of systemic lupus erythematosus (SLE). This single-arm, open-label, phase 2 clinical trial aims to evaluate the safety and efficacy of the ASC-depleting anti-CD38 monoclonal antibody daratumumab in patients with SLE (NCT04810754). The primary endpoint is the reduction in serum anti-double-stranded DNA (anti-dsDNA) antibody levels at week 12. Key secondary end points include safety, clinical efficacy, and immunologic changes. Ten female patients with active disease and inadequate responses to at least two immunosuppressive drugs have received eight subcutaneous injections of 1800 mg daratumumab weekly, with dexamethasone as premedication (20 mg for first two injections, then 10 mg). By week 12, anti-dsDNA antibody levels have been reduced by a median of 109.6 IU/ml (95% CI 38.1 – 274.5). The treatment resulted in rapid and sustained clinical improvements across all patients and organ domains, reflected by a 100% SRI-4 (Systemic Lupus Erythematosus Responder Index-4) response rate at week 12. Hypogammaglobulinemia occurred in 5/10 patients, requiring immunoglobulin substitution. Daratumumab treatment has depleted circulating ASCs, reduced type I interferon activity, and profoundly modulated the T-cell responses. These findings highlight the pivotal role of ASCs in SLE pathogenesis and support daratumumab as therapeutic option for SLE.

CD38 is highly expressed by antibody-secreting cells (ASC) and depleting antibodies targeting CD38 have the potential to treat autoimmune diseases with ASC involvement. Here authors treat systemic lupus erythematosus patients with the ASC-depleting anti-CD38 monoclonal antibody daratumumab in addition to dexamethasone in the frame of a single arm, open-label phase 2 clinical trial to show marked improvements in their clinical and immunological status.