Abstract: TH-PO1265
A Phase 2 Open-Label Trial Evaluating the Efficacy and Safety of Daratumumab (Dara) in Treatment of Patients with Active Lupus Nephritis (LN)
Session Information
- Late-Breaking Research Posters
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Zand, Ladan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Vargas-Brochero, Maria J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Duarte-Garcia, Ali, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Despite standard immunosuppressive therapy, 10-30% of patients with LN progress to ESKD & up to 50% fail treatment, highlighting need for novel therapies. Plasma cell targeting with Dara (anti-CD38) has shown promise in small LN case series.
Methods
9 patients with active class III, IV or V LN received SC Dara (1800 mg) x 16 doses over 6 m on background MMF (1.4 g/d IQR 1-2g/d). Primary endpoint: proportion of patients achieving renal response (RR) at 12m. PRR: ≥50% reduction in proteinuria, inactive sediment (<10 RBC/HPF), ≤ 20% decline in eGFR. CRR: proteinuria < 500 mg, inactive sediment, ≤ 15% decline in eGFR. Secondary endpoints were incidence of major infections, changes in proteinuria, eGFR, anti-dsDNA, and complement levels at 6, 12 and 24 m.
Results
Mean age was 36.4 ± 10.9 years & 8 were female. LN: class III/IV ± V (n=7), V (n=2). Average sBP :123.4 ± 10.1, dBP: 78.9 ± 7.5. Two withdrew at 12m due to lack of response. At 6m there was significant improvement in anti-dsDNA, C3/C4, eGFR & albumin (Table 1). At 12 m there was significant reduction in proteinuria with 66.7% having a RR (4 CRR, 2 PRR). Of 7 completing 24 m, 4 relapsed and were retreated with Dara (OLE). Two hospitalizations occurred (LN flare and Bactrim allergy). Total of 21 infections, most common: COVID 19, influenza, bronchitis & UTI. Infections were mild and did not result in Dara discontinuation.
Conclusion
Dara was associated with rapid improvement in lupus serology and eGFR at 6m translating into significant RR at 12 m. However, relapse in 4/6 responders suggests that although Dara is effective for LN, additional data is needed to evaluate the role of Dara-based maintenance therapy to sustain remission.
Laboratory and urinary data at baseline and post-Dara
| Parameter | Baseline (n=9) | 6 months (n=9) | P value | 12 months (n=7) | P value | 24 months | P value |
| eGFR (CKD-EPI) (ml/min/1.73m2) Serum Albumin (g/dL) | 75.8 ± 24.8 3.2 ± 0.7 | 96.1 ± 25.4 3.7 ± 0.8 | 0.02 0.04 | 85.3 ± 22.3 4.0 ± 0.3 | 0.016 0.04 | 81.1 ± 24.0 3.8 ± 0.4 | 0.44 0.03 |
| C3 (mg/dL) C4 (mg/dL) | 72.1 ± 31.7 11.4 ± 5.6 | 95.9 ± 19.4 16.9 ± 7.3 | 0.02 0.02 | 94.4 ± 17.9 18.1 ± 7.4 | 0.12 0.09 | 88.1 ± 32.3 18.4 ± 8.0 | 0.42 0.15 |
| Anti-ds-DNA (IU/ml) Proteinuria (g/24hour) | 64.8 (52.9, 236.0) 2.5 (1.1, 3.8) | 36.6 (18.2, 78.0) 1.0 (0.4, 1.8) | 0.02 0.07 | 12.3 (12.3, 101.7) 0.2 (0.2, 0.5) | 0.46 0.02 | 26.3 (16.6, 153.5) 1.5 (0.3, 2.1) | 0.58 0.17 |
Data are presented as mean ± SD unless otherwise indicated. Anti-ds-DNA and proteinuria are presented as median (IQR). Paired t-tests were used for normally distributed continuous variables. Wilcoxon signed-rank tests were used for anti-ds-DNA at 6 and 12 months, proteinuria at 6 and 12 months, serum albumin at 6 and 12 months. Anti-ds-DNA (negative <30 IU/ml), C3 normal range (75-175 mg/dL), C4 normal range (14-40 mg/dL)
Funding
- Commercial Support – Janssen Pharmaceutical