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Abstract: FR-PO669

Novel Treatment Option for PLA2R-Positive Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Sen, Aditi A., Baylor College of Medicine, Houston, Texas, United States
  • Aggarwal, Nidhi, Baylor College of Medicine, Houston, Texas, United States
  • Yellapragada, Sarvari, Baylor College of Medicine, Houston, Texas, United States
  • Mbue, John E., Michael E DeBakey VA Medical Center, Houston, Texas, United States
  • Shah, Maulin, Baylor College of Medicine, Houston, Texas, United States
Introduction

B-cell depletion with rituximab has been shown to be effective in treating anti-phospholipase A2 receptor (aPLA2R) antibody-associated membranous nephropathy (MN). While rituximab is generally well tolerated, some patients may develop serious side effects limiting its use. Novel anti-CD20 agents are now available, but evidence of their effectiveness in aPLA2R-MN is limited. We present a case of aPLA2R-MN treated with ofatumumab.

Case Description

A 45-year-old man presented with recurrence of MN. He had Hodgkin’s lymphoma at age 14 and underwent splenectomy and chemotherapy (MOPP/ABVD regimen) which caused neuropathy. Sixteen years later, he developed polymorphous large cell lymphocytosis, a complication of prior chemotherapy and splenectomy. He first developed membranous nephropathy in 2014 (age 38), which was successfully treated with rituximab. He had recurrent membranous nephropathy (2017) with biopsy revealing aPLAR2 (serum level 37 RU/mL) and again achieved remission with rituximab. Subsequently, he developed worsening neuropathy, likely due to rituximab. He had another recurrence (2020), initially treated with cyclosporine but was not effective (aPLA2R level 110.5 RU/mL). Given prior response to anti-CD20 therapy and given high risk of side-effects with cyclophosphamide, we opted to treat with ofatumumab (no known reports of neuropathy) guided by B-cell depletion confirmation. Three months after treatment, he has achieved serological remission and shown significant improvement in proteinuria.

Discussion

This case highlights that novel anti-CD20 agents may be considered for aPLA2R-MN when use of rituximab is prohibitive. Rituximab, a chimeric monoclonal antibody, may cause development of human anti-chimeric antibodies, which can affect efficacy and tolerability. Novel agents, such as ofatumumab, being fully human or humanized, decrease immunogenicity. Many of them have boosted efficacy due to increased binding affinity to Fc receptor on B-cells with increased complement-dependent cytotoxicity and/or antibody-dependent cellular cytotoxicity. It remains to be seen if our patient achieves complete and persistent remission. Further studies are needed to investigate the ability of these agents to achieve and maintain serological and clinical remission in aPLA2R-MN and understand their overall tolerability.