Abstract: TH-PO1207
A Phase 2 Open-Label Trial Evaluating the Efficacy and Safety of Daratumumab in Treatment of Patients with Proliferative Glomerulonephritis with Monoclonal Immune Deposits (PGNMID)
Session Information
- Late-Breaking Clinical Trials Posters
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Zand, Ladan, Mayo Clinic, Rochester, Minnesota, United States
- Leung, Nelson, Mayo Clinic, Rochester, Minnesota, United States
- Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States
- Rajkumar, S. Vincent, Mayo Clinic, Rochester, Minnesota, United States
- Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
Background
PGNMID is the result of the direct deposition of monoclonal proteins in the kidney and the ensuing inflammation. There are no proven therapies available. Rituximab or combination of cyclophosphamide, bortezomib & dexamethasone have been used with variable success.
Methods
In this trial we evaluated the safety & efficacy of daratumumab (an anti-CD38 plasma therapy). The primary safety end point was incidence of major infections, grade 3 or 4 pancytopenias. The primary efficacy end point was rate of complete remission (CR) (proteinuria <300 mg & <10% drop in eGFR) or partial remission (PR) (50% reduction in proteinuria & <30% drop in eGFR). Patients were treated with daratumumab IV at a dose of 16mg/kg once weekly for 8 weeks followed by once every other week for an additional 8 doses.
Results
Total of 9 patients were recruited. The mean age was 53.6±20.3 years. There were 5 males. Two withdrew from the study. At the end of treatment (6 m) the median 24hr urinary protein (UP) declined from 6.0g (IQ 4.4-8.2) to 0.64g (0.5-3.0), p=0.003 with a corresponding rise in serum albumin from 2.98±0.63 to 3.75±0.84 g/dL (p=0.03). Serum creatinine showed improvement from 1.52 ± 0.52 to 1.39 ± 0.47 mg/dL (p=0.1). At 6m, of the 7 patients, 1 achieved CR and 4 achieved PR. In 5 patients who had 12m data available, median 24hr UP at 6m was 3.0g (IQ 0.5-4.3) which decreased significantly from baseline, p=0.01. Median 24hr UP at 12 m was lower at 1.29 (IQ 0.3-4.0), p=0.01. Mean serum creatinine at 12 m was 1.15 ± 0.32 and unchanged from 6m (1.18±0.35, p=0.1). Four of the 5 achieved PR at 12 m. There were two serious adverse events. One was acute glaucoma which occurred 45 min into 1st infusion (patient was withdrawn). Another was eye chemosis/headache after receiving one infusion. Patient withdrew, but 2 m after, the 24hr UP showed no proteinuria (baseline of 2.3 g/24hr). The most common side effects were infusion-related reactions. There were no major infections or pancytopenias.
Conclusion
In this trial, daratumumab was shown to be effective in reducing proteinuria dramatically in patients with PGNMID along with stabilization of renal function. The effect is sustained at 12 m. In conclusion daratumumab is a promising therapy for treatment of patient with PGNMID.
Funding
- Commercial Support –