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Daratumumab monotherapy for refractory lupus nephritis
Dario Roccatello1, Roberta Fenoglio2, Ilaria Caniggia2
1University Center of Excellence on Nephrological, Rheumatological and Rare Diseases (ERK-net, ERN-Reconnect and RITA-ERN Member) including Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital, ASL Città di Torino and Department of Clinical and Biological Sciences of the University of Turin, Turin, Italy. dario.roccatello@unito.it.
Daratumumab, an anti-CD38 antibody, showed promise in treating refractory lupus nephritis (LN). Five of six patients experienced reduced disease activity, proteinuria, and improved kidney function after 12 months.
Area of Science:
- Immunology
- Nephrology
- Rheumatology
Background:
- Treatment-refractory lupus nephritis (LN) presents a significant risk of poor outcomes and can be life-threatening.
- Current therapeutic options for refractory LN are limited, necessitating the exploration of novel treatment strategies.
Observation:
- A case series involved six patients with biopsy-proven refractory LN, with a median age of 41.3 years.
- Patients received intravenous daratumumab, an anti-CD38 monoclonal antibody, over a period of up to 8 months.
Findings:
- One patient showed no improvement and discontinued therapy.
- In the remaining five patients, significant improvements were observed at 12 months, including decreased SLEDAI scores (10.8 to 3.6), reduced proteinuria (5.6g/24h to 0.8g/24h), and lower serum creatinine (2.3mg/dL to 1.5mg/dL).
- Clinical improvements correlated with seroconversion of anti-dsDNA antibodies, decreased interferon-gamma, B cell maturation antigen, and soluble CD163 levels, alongside increased C4 and IL-10 levels.
Implications:
- Daratumumab monotherapy demonstrates potential as a therapeutic option for patients with refractory lupus nephritis.
- Further clinical trials are warranted to validate these findings and establish the efficacy and safety of daratumumab in a larger cohort.
- This study highlights the immunomodulatory effects of anti-CD38 antibodies in autoimmune kidney diseases.
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