Abstract: FR-PO0690
Differing Phospholipase A2 Receptor (PLA2R) Antibody Decline Kinetics After Obinutuzumab in High-Risk Membranous Nephropathy: Report of Two Cases
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 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
- Tan, Shi Yun, Singapore General Hospital, Singapore, Singapore
- Choo Chon Jun, Jason, Singapore General Hospital, Singapore, Singapore
- Loo, Kok pan, Singapore General Hospital, Singapore, Singapore
- Wong, Jiunn, Singapore General Hospital, Singapore, Singapore
- Tan, Hui Zhuan, Singapore General Hospital, Singapore, Singapore
Introduction
Obinutuzumab (OBI) is an emerging option for PLA2R membranous nephropathy (MN), particularly in patients who have failed prior therapies. In high-risk disease, rapid antibody (ab) reduction is desired, but the optimal dosing strategy of this high-cost therapy remains unclear. We present 2 cases of high-risk PLA2R MN who received OBI with positive but variable treatment trajectories.
Case Description
A 59-year-old male with high-risk MN (anti-PLA2R ab 354.8 RU/ml; sCr 168µmol/L; sAlb 17g/L; uPCR 18.77g/g) and virally suppressed HIV on Biktarvy, was given OBI after suboptimal response with Rituximab (RTX) 2g. Titres plateaued at 3m after initial 1g OBI (271>142 RU/ml), necessitating repeat dosing; persistent elevation (7RU/ml; target <2) led to a third 1g at 11 months. HIV RNA load was 28 copies/ml prior to B-cell depleting therapies and remained suppressed, with stable CD4 counts throughout.
A 58-year-old male with high-risk MN (anti-PLA2R ab 968 RU/ml; sCr 97µmol/L; sAlb 24G/L; 24hr UTP 6.3g/day) was given RTX 2g with suboptimal immunological (338 RU/ml) and clinical response (sCr 136µmol/; sAlb 21G/L; 24hr UTP 11.1g/day) at 6m. CYC did not result in sustained remission. OBI 1g was given with rapid immunological response over 3m (318.2 > 13.65 RU/ml; sCr 130µmol/L; sAlb 24g/L; uPCR 9.87g/g). Titres and response are closely monitored to guide further dosing.
Discussion
Both high-risk MN patients demonstrated favorable immunologic responses to OBI, with similar directions of PLA2R ab decline but differing rates, highlighting variability in response kinetics despite high baseline titres and expected induction needs. This variability underscores the limitations of relying solely on antibody titres to guide dosing, as comparable serologic profiles may still be associated with different clinical trajectories. Given the high cost of OBI, these findings support a response-guided approach over fixed regimens, offering potential cost savings without compromising efficacy. OBI was well tolerated in the HIV-positive patient, with no adverse virologic or immunologic effects, contributing to limited safety data in this population. Overall, these cases support response-guided OBI dosing in high-risk PLA2R MN refractory to conventional therapy and suggest acceptable safety in HIV-positive patients, although prospective studies are needed to establish individualized dosing strategies.