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Abstract: FR-PO665

Refractory Membranous Nephropathy With Anti-Rituximab Antibodies Treated Successfully With Obinutuzumab

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Author

  • Kumar, Sumit, Texas Kidney Institute, Dallas, Texas, United States
Introduction

Membranous nephropathy results from IgG deposition in glomerular capillaries. A precision-medicine based anti-CD 20 approach has continued to evolve. Rituximab (RTX), has become the cornerstone for treatment after it’s demonstration to be noninferior to cyclosporine. Here, we report anti-rituximab antibodies causing rapidly refractory disease, successfully treated with Obinutuzumab (OZB)

Case Description

A 65 yr old Caucasian male presented in Nov 2017 with shortness of breath. An acute pulmonary embolism and renal vein thrombosis was diagnosed with 25 g proteinuria and normal renal function. Kidney Biopsy demonstrated Idiopathic membranous nephropathy with No crescents, fibrinoid necrosis, thrombosis or endocapillary hypercellularity. Initial treatment was pulse steroids in Jan 2018 and 1 dose of RTX 1 gram. 2nd dose was never given. He went into a remission and came to our care in Oct 2019. In Mar 2020, he relapsed and underwent RTX infusion 1 g every 2 weeks for 2 doses. His initial response over the next few months was favorable, but he relapsed 4 months later. Other than trace to 1+ edema, he remained asymptomatic. Anti-RTX Antibody was 158 ng/mL. He was treated with OZB – Day 1 – 100 mg; Day 2 – 900 mg and Day 8 – 1000 mg, along with hypersensitivity prophylaxis. His Anti PLA 2R Ab became undetectable in 3 months and UPCR dropped steadily. He has remained asymptomatic, without any recurrence of proteinuria in extended follow-up.

Discussion

Our patient presented a unique conundrum with steady clinical improvement after being treated with rituximab, and then developing rapid relapse with detection of anti-rituximab antibodies. In our review, this has not been described previously. Obinutuzumab, fully humanized type II anti-CD 20 monoclonal antibody produces greater CD20 depletion and is superior to rituximab. While the use of Obinutuzumab has been described in limited case reports for the treatment of refractory membranous nephropathy, anti-rituximab antibodies have not been described in refractory disease.

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