Abstract: SA-PO0653
Safety and Efficacy of Belzutifan for von Hippel-Lindau Disease-Associated Renal Cell Carcinoma
Session Information
- Monogenic Kidney Diseases: Tubular and Other
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Ge, Peixi, Johns Hopkins University Zanvyl Krieger School of Arts and Sciences, Baltimore, Maryland, United States
- Atta, Mohamed G., Johns Hopkins Medicine, Baltimore, Maryland, United States
- Srialluri, Nityasree, Johns Hopkins Medicine, Baltimore, Maryland, United States
Background
Von Hippel–Lindau (VHL) disease is a rare hereditary syndrome causing a lifelong risk of clear cell renal cell carcinoma (RCC). Belzutifan, a hypoxia-inducible factor-2α inhibitor, received FDA approval in 2021 for adults with VHL-associated RCC. While the phase 2 data demonstrated a 49% objective response rate by RECIST v1.1, real-world evidence remains limited. We evaluated the safety and efficacy of belzutifan in a real-world cohort, focusing specifically on kidney manifestations.
Methods
We conducted a retrospective analysis of adults (≥18 years) with genetically or clinically confirmed VHL at Johns Hopkins Hospital between January 2016- December 2024. Inclusion criteria required treatment with belzutifan, at least one kidney lesion, and post-treatment imaging. Demographic and clinical data were extracted from EMR. Baseline and follow-up tumor and cyst characteristics were assessed by CT or MRI. Response treatment was assessed and evaluated per RECIST v1.1. Additional variables included treatment duration, adverse events (AEs), and therapy discontinuation.
Results
10 patients were included (mean±SD age 38±13 years; 70% female). Median treatment duration was 31 months (IQR 29-39). 4 patients (40%) had partial responses; 4 (40%) had stable disease; 2 (20%) had disease progression; 0 had complete response. Both progression events occurred following prolonged treatment interruption. One patient missed doses intermittently, and the other discontinued due to pregnancy planning. At one year, 6 patients demonstrated tumor regression; 3 achieved ≥30% reduction (maximum decrease 45.5%). AEs included: anemia (30%), headache (30%), and dizziness (20%). No discontinuations were due to AEs.
Conclusion
In this real-world cohort of patients with VHL-associated RCC, belzutifan demonstrated a favorable safety profile and showed a 40% objective response rate, comparable to that reported in clinical trials. Tumor progression was associated with treatment interruption. These findings support the clinical utility of belzutifan and underscore the need for larger studies to inform long-term management of kidney manifestations in VHL.