Abstract: FR-PO1252
Pegcetacoplan for Lenvatinib-Associated Thrombotic Microangiopathy
Session Information
- Onconephrology: Diagnostic Dilemmas, Therapy-Related Toxicities, and Clinical Cases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Kuruvada, Krishna Mohita, Northwell Health, New Hyde Park, New York, United States
- Wu, Ming, Northwell Health, New Hyde Park, New York, United States
- Jhaveri, Kenar D., Northwell Health, New Hyde Park, New York, United States
Introduction
Tyrosine kinase inhibitors(TKI) are increasingly recognized causes of thrombotic microangiopathy (TMA) and other podocytopathies. Complement activation has been implicated in secondary TMAs. We present a case of lenvatinib-associated TMA and podocytopathy that demonstrated improvement following treatment with pegcetacoplan, a C3 inhibitor.
Case Description
A 67-year-old man with hypertension and metastatic thyroid cancer treated with lenvatinib was referred for evaluation of progressive proteinuria and edema. He developed nephrotic syndrome and kidney dysfunction while on therapy. Initial urine protein-to-creatinine ratio (UPCR) was approximately 4.3 g/g and progressively worsened, eventually exceeding 8 g/g requiring hospitalization for nephrotic syndrome and severe edema. Serum creatinine increased from a baseline of 0.97 mg/dL to a peak of 2.04 mg/dL A kidney biopsy demonstrated TMA with concurrent diffuse podocytopathy attributed to lenvatinib. Initial management included eculizumab therapy. After 6 months of therapy, the nephrotic syndrome and kidney dysfunction persisted despite treatment. Lenvatinib was subsequently discontinued because of ongoing renal toxicity. Given the original kidney biopsy had potential podocytopathy as well, a trial of 2 months of steroids was attempted with no success. A repeat kidney biopsy yielded ongoing chronic TMA with no features of podocytopathy and increased fibrosis. The SC5b-9 Complement complex was worsening. Given refractory disease, the patient initiated pegcetacoplan using a dosing schedule like C3 glomerulopathy protocols. Following 3 months of treatment, proteinuria improved substantially, with UPCR decreasing from nephrotic range to approximately 0.8 g/g. Serum creatinine improved from 2.04 mg/dL to 1.89 mg/dL with stabilization of kidney function and improvement in edema, while serum albumin increased from 3.2 g/dL to 4.2 g/dL. The patient is planned for ongoing treatment with pegcetacoplan for total of 9 months.
Discussion
This case highlights severe lenvatinib-associated kidney toxicity manifesting as dual pathology with TMA and podocytopathy. To our knowledge, this represents one of the first reports describing the use of pegcetacoplan for refractory drug induced TMA. The marked reduction in proteinuria following treatment suggests a potential therapeutic role for proximal complement inhibition in selected cases of secondary TMAs.