Abstract: TH-PO0773
Daratumumab in Refractory Membranous Nephropathy: A Report of Four Cases
Session Information
- Glomerular Case Reports: Membranous, PGN, GBM, and More
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Bilen, Yara, Penn Medicine, Philadelphia, Pennsylvania, United States
- Fischman, Clara, Penn Medicine, Philadelphia, Pennsylvania, United States
- Geara, Abdallah Sassine, Penn Medicine, Philadelphia, Pennsylvania, United States
Introduction
Membranous nephropathy (MN) is a leading cause of adult nephrotic syndrome, characterized by subepithelial immune complex deposition and podocyte injury. Several autoantibodies are implicated in pathogenesis and B-cell depletion using anti-CD20 monoclonal antibodies (mAb) are the cornerstone of therapy. A subset of patients remains refractory to rituximab or obinutuzumab. Daratumumab, an anti-CD38 mAb, is emerging as a promising therapy for several B-cell mediated diseases by targeting long-lived plasma cells.
Case Description
We report a case series of four patients with biopsy-proven anti-PLA2R-associated MN refractory to at least two agents, rituximab, obinutuzumab or cyclophosphamide, and who received daratumumab with hyaluronidase-fihj 1800 mg s/c weekly. Treatment course and outcomes are summarized in the table. All 4 patients were classified as high-risk disease with nephrotic syndrome and progressive kidney dysfunction. In three patients, we observed quick immunologic remission with undetectable anti-PLA2R within the first month. Patient #4 had very low levels of anti-PLA2R by ELISA and IFA and is still undergoing therapy with variable response. The therapy was associated with 2 infectious complications: ophthalmic zoster for one patient who was not on acyclovir prophylaxis and pneumonia that did not require hospitalization.
Discussion
Daratumumab has shown effectiveness in reducing proteinuria and improving serologic markers in patients with refractory MN. Additionally, it demonstrated a favorable safety profile in a small cohort. These promising findings support the need for further investigations through clinical trials to better understand the potential benefits and broader applicability of anti-CD38 mAb in treating MN.
Summary of patient demographics, treatment course and outcomes.