Abstract: FR-PO0752
Obinutuzumab as a Rescue Therapy for Rituximab-Refractory NELL-1-Positive Membranous Nephropathy After Allogeneic Stem-Cell Transplantation
Session Information
- Glomerular Diseases: ANCA Vasculitis, Anti-GBM Disease, and Crescentic GN
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
- Shah, Ali, The University of Chicago Medicine, Chicago, Illinois, United States
- Bonilla, Marco, The University of Chicago Medicine, Chicago, Illinois, United States
Introduction
NELL1-positive membranous nephropathy (MN), a type of nephrotic syndrome often linked to malignancy, with limited data on optimal treatment. This is true especially in post-allogenic stem cell transplant (alloSCT). B cell depletion is standard therapy for primary MN. We present a case of rituximab resistant NELL-1 MN post alloSCT that was managed with obinutuzumab.
Case Description
63 yr-old male with history of relapsed AML s/p alloSCT who presented with nephrotic syndrome. On arrival, UPCR 9.6g/g, serum albumin 1.9 g/dl, cholesterol 221 and anasarca. Kidney Biopsy revealed MN with mild IFTA, with NELL-1 positivity by immunohistochemistry. During the course, patient developed AKI with creatinine (Cr) peaking at 2.48 mg/dL (baseline 1.5). Patient was initially treated with diuretics, anticoagulation, angiotensin receptor blocker, and started on Rituximab at a dose of 1g IV on day 0 and day 14. However, B-cell suppression was not achieved, & remained in refractory nephrotic range proteinuria and hypoalbuminemia at 6months. Given treatment failure, Obinutuzumab was started at a dose of 1g on day 0 & day 14. This resulted in a dramatic clinical response and complete remission of proteinuria (UPCR dropping to 0.2 g/g), normalization of serum albumin and discontinuation of diuretics and anti-coagulation. Cr also improved to 1.3 mg/dl.
Discussion
NELL1-positive MN in the post-alloSCT setting likely represents a distinct form of GVHD associated nephropathy, with graft-derived antibodies targeting host podocyte antigens. Rarity of this condition, reported in only 2 of 9 post-HSCT MGN cases in published series, means treatment strategies remain largely undefined. Our case demonstrates that rituximab failure may be driven by inadequate B-cell depletion, and that obinutuzumab, a type II anti-CD20 antibody with superior B-cell cytotoxicity, can achieve meaningful clinical response in this setting. This shows obinutuzumab as an effective rescue therapy in rituximab-refractory NELL1-positive MN and highlights the need for prospective studies to define optimal B-cell targeting strategies in the post-transplant setting.
| Parameters | Baseline | Post-Rituximab (6months) | Post-Obinutuzumab (6 months) |
| Proteinuria (g/24h) | 9.6 | 10.4 | 1.6 |
| Albumin (g/dL) | 1.9 | 2.5 | 3.9 |
| CD19count (cells/µL) | 20.38 | 99.84 | 0.00 |
| Creatinine (mg/dl) | 1.5 | 2.48 | 1.48 |