Abstract: FR-PO668
Screening for Anti-Rituximab Antibody in Management of Rituximab Refractory PLA2R-Associated Membranous Nephropathy
Session Information
- Glomerular Diseases: Clinical, Outcomes, Trials - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials
Authors
- Ositelu, Ayotunde, Northwestern Memorial Hospital, Chicago, Illinois, United States
- Vissing, Andrew, Northwestern Memorial Hospital, Chicago, Illinois, United States
- Ayoub, Wadah Jason, Northwestern Memorial Hospital, Chicago, Illinois, United States
- Peleg, Yonatan A., Northwestern Memorial Hospital, Chicago, Illinois, United States
- Kanwar, Yashpal S., Northwestern Memorial Hospital, Chicago, Illinois, United States
- Aggarwal, Vikram, Northwestern Memorial Hospital, Chicago, Illinois, United States
Introduction
Phospholipase A2 receptor associated Membranous Nephropathy (PLA2R-MN) accounts for 80% of primary MN (pMN). High titers of anti-PLA2R-Ab and non-remission of Nephrotic syndrome (NS) are associated with poor renal outcomes. Rituximab (RTX), a chimeric monoclonal antibody (mAb) targeting CD20 on B-cells, is a first-line agent for moderate to high-risk pMN. However,20-40% of pMN remain refractory to RTX.We report an approach to manage RTX refractory PLA2R-MN based on the use of the anti-RTX Ab assay.
Case Description
A 78 year-old male presented to our Nephrology clinic to manage severe N.S. He was on high dose of diuretics and ACEI for 3 months. Evaluation revealed proteinuria of 15 g/day, serum albumin (S. A) of 2 g/dl, eGFR=47 ml/min and anti-PLA2R Ab level was 751.6 RU/mL (positive test > 20 RU/ml). Renal biopsy findings were consistent with MN. He met high-risk criteria for pMN and received RTX 1g i.v twice within 2 weeks.3 months later, anti-PLA2R levels decreased to 48.1 RU/mL. At 6 months he had partial remission (P.R) of proteinuria, improvement in edema and S.A remained 3-3.3 g/dl. Overall suggesting RTX-responsive course however due to lack of immunologic remission (I.R) he received RTX(1g) at 6 months. We noticed worsening of proteinuria and edema at 8 months. Anti-PLA2R level had risen serially up to 794.6 RU/mL at 10 months. Lack of I.R (refractory pMN) and worsening N.S prompted us to investigate factors contributing to RTX resistance and reduced bioavailability. We screened him for neutralizing Abs against RTX and his anti-RTX Ab level was elevated: 1,432 ng/mL (normal < 25 ng/mL) and he had undetectable RTX level. We obtained approval and he received Obinutuzumab (OBI, fully humanized mAb) at 12 months. OBI is directed to a different epitope on CD20 and has higher affinity for CD20 than RTX. Within a month of OBI, anti-PLA2R Ab came down to 25 RU/mL.UPCR was 2.19 g/g & S.A 3.5 g/dL at 14 months thus denoting P.R and near complete I.R.
Discussion
This case report highlights the clinical utility of anti-RTX Ab screening when managing patients with refractory PLA2R-MN. The presence of anti-RTX should prompt the use of new generation (more humanized) anti-CD20 therapy to achieve immunologic and clinical remission.