Abstract: FR-PO1243
Collapsing FSGS After B7-H4-Targeted Antibody Drug Conjugate Therapy
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
- Al Haddad, Nadia, Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Yang, Yihe, Weill Cornell Medicine, New York, New York, United States
- Latcha, Sheron, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Introduction
Antibody drug conjugates (ADCs) consist of an antibody, a linker and a cytotoxic payload that target specific tumor antigens and release cytotoxic drugs directly into a cancer cell, sparing non cancer tissue.B7-H4 is an immunosuppressive protein that is overexpressed in certain cancers and which allows tumors to escape immune destruction.B7-H4 is also expressed in renal tubular cells, podocytes and glomerular endothelial cells.
Case Description
A 50-year-old woman with recurrent metastatic adenoid cystic carcinoma was enrolled in a clinical trial with XMT-1660. After cycle 1, she developed 1+ proteinuria; after cycle 2, 3+ proteinuria with hematuria; and after cycle 3, new onset hypertension with periorbital and lower extremity edema, and ascites. 24H urine protein was 11.8g, albumin 2.5g/dl, total cholesterol 557, schistocytes on peripheral smear, haptoglobin 427 mg/dl.
Serologic workup was negative, including anti-dsDNA, complement levels, ANCA, anti-PLA2R, THSD7A, ANA, hepatitis serologies, HIV, rheumatoid factor, cryoglobulins, serum free light chains, serum protein electrophoresis, and immunofixation.
Kidney biopsy demonstrated collapsing focal segmental glomerulosclerosis (17/67), global glomerulosclerosis (23/67), 20–30% interstitial fibrosis (Figure 1).
The study drug was discontinued. Prednisone (1mg/kg) and losartan decreased proteinuria to 7.4g. After addition of cyclosporine, 24H protein improved to 0.4 g/day.
Discussion
This case identifies collapsing FSGS as a potential complication of B7-H4 targeted ADC therapy. B7-H4 is expressed on renal tubular epithelial cells and prior studies suggest its activation contributes to tubular injury and immune modulation. Targeting this pathway may disrupt local immune homeostasis or induce off-target toxicity, resulting in podocyte injury. The temporal association, absence of alternative etiologies, and treatment response support an immune-mediated, drug-induced process.Further studies are needed to clarify mechanisms and management.
A-B: LM: collapsing glomerulopathy C: IF: no deposits D-E: EM: preserved foot processes