Abstract: TH-PO586
Belimumab and Rituximab for the Treatment of Primary Membranous Nephropathy: Initial REBOOT Results
Session Information
- Membranous Nephropathy, FSGS, and Minimal Change Disease
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Nachman, Patrick H., University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Stelzig, Lia, Rho Inc., Durham, North Carolina, United States
- Sherman, Matthew A., National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States
- Barry, William T., Rho Inc., Durham, North Carolina, United States
- Chung, Sharon, University of California San Francisco, San Francisco, California, United States
Group or Team Name
- On behalf of the REBOOT Study Investigators.
Background
Primary membranous nephropathy (PMN) is caused by glomerular immune complex deposition, and 70% of patients produce anti-phospholipase A2 receptor (PLA2R) autoantibodies. We hypothesize that treatment with belimumab (BEL) and rituximab (RTX) will enhance memory B cell depletion, curb the re-emergence of autoreactive B cells, and lead to better clinical responses compared to RTX alone.
Methods
REBOOT (NCT03949855) is a two-part, phase 2, multicenter, clinical trial examining the effectiveness of BEL with RTX for the treatment of PMN. Participants (18-75 years) must have detectable serum anti-PLA2R and proteinuria ≥ 4 g/d. Part A is a single arm, open-label, pharmacokinetic study, where all participants receive BEL 200 mg weekly for 52 weeks and RTX 1000 mg at weeks 4 and 6. Participants are followed for complete (CR, proteinuria ≤ 0.3 g/d with serum albumin ≥ 3.5 g/dL) or partial remission (PR, proteinuria < 3.5 g/d with ≥50% reduction from baseline) to week 156. We present the initial clinical results for Part A.
Results
17 participants (mean age 56 years) started BEL and RTX; 5 stopped BEL prior to week 52 (COVID-19 [n=2]; infection, mood swings, worsening kidney function [1 each]). 9 participants have completed BEL and reached week 104 so far. Table 1 presents baseline characteristics and clinical outcomes. 89% (8/9) achieved CR or PR by week 104. The proteinuria decline, anti-PLA2R reduction, and serum albumin normalization persisted for 1 year after stopping BEL without additional RTX or other immunotherapy.
Conclusion
A large proportion of evaluable participants have attained PR or CR with BEL and RTX so far. A rapid decline in anti-PLA2R and normalization of serum albumin also occurs. Part A followup continues, and Part B, a randomized, double-blind, placebo-controlled trial comparing BEL with RTX to RTX alone, is enrolling to assess the effectiveness of this treatment strategy.
Clinical Outcomes for REBOOT Part A.
| Timepoint (# evaluable participants) | Baseline (n=17) | Week 24 (n=13) | Week 52 (n=12) | Week 104 (n=9) |
| CR or PR (% achieved) | 0 | 23 | 67 | 89 |
| Anti-PLA2R (% detectable) | 100 | 15 | 17 | 0 |
| Proteinuria (g/d), median (interquartile range) | 11.2 (8.2-16.7) | 5.5 (3.7-9.3) | 2.1 (1.1-4.9) | 1.0 (0.5-2.7) |
| Serum albumin (g/dL), median (interquartile range) | 2.6 (2.3-2.9) | 3.6 (3.3-3.7) | 4.1 (3.8-4.3) | 4.3 (4.2-4.5) |
| Serum creatinine (mg/dL), mean (standard deviation) | 1.2 (0.3) | 1.3 (0.4) | 1.1 (0.4) | 1.2 (0.2) |
Anti-PLA2R = anti-phospholipase A2 receptor autoantibody, CR = complete remission, PR = partial remission
Funding
- Other NIH Support – Belimumab was provided by GSK plc.