Clinical Outcomes of HIF-2α inhibition in Von Hippel-Lindau Disease: A Multicenter Real-World Study

Mousab Al Abbas; Jabra Zarka; Alvin C Silva; Filippo Cingolani; Muhammed Uzair Sarfraz; Albert Jang; Muhammad Ali Khan; Fouad Nahhat; Winston Tan; Brian A Costello; Haidar Abdul-Muhsin; Irbaz Bin Riaz; Yousef Zakharia

doi:10.1093/oncolo/oyag331

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Clinical Outcomes of HIF-2α inhibition in Von Hippel-Lindau Disease: A Multicenter Real-World Study

Journal article

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Clinical Outcomes of HIF-2α inhibition in Von Hippel-Lindau Disease: A Multicenter Real-World Study

Mousab Al Abbas, Jabra Zarka, Alvin C Silva, Filippo Cingolani, Muhammed Uzair Sarfraz, Albert Jang, Muhammad Ali Khan, Fouad Nahhat, Winston Tan, Brian A Costello, …

The oncologist (Dayton, Ohio), Vol.31(10), oyag331

08/18/2026

DOI: 10.1093/oncolo/oyag331

PMID: 42610708

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Abstract

Management of von Hippel-Lindau (VHL) disease is challenging due to multisystem involvement and limited systemic treatment options. Belzutifan has shown promising efficacy in clinical trials; however, real-world data remain limited. We aimed to evaluate its effectiveness and safety in a real-world cohort. We conducted a retrospective study of 59 patients with VHL disease treated with belzutifan between August 2021 and January 2026. Objective response rates (ORR) for renal cell carcinoma (RCC), central nervous system hemangioblastomas (CNS HB), and pancreatic neuroendocrine tumors (pNET) were assessed by an independent radiologist. Retinal hemangioblastoma outcomes were evaluated through ophthalmology records by chart review. Median follow-up was 29 months. ORR was 27.6%, 39.6%, and 85.7% for RCC, CNS HB, and pNET, respectively. Among 13 patients with retinal hemangioblastomas (20 eyes), 17 eyes (85%) showed improvement.At data cutoff, 47 patients (79.6%) remained on treatment, while 12 (20.3%) discontinued (7 due to adverse events, 3 to disease progression, and 2 to other reasons). The most common adverse event was anemia (86.4%). Grade ≥3 events occurred in 10 patients (16.9%).The procedure rate per patient-year decreased from 0.35 in the 3 years prior to treatment to 0.08 during follow-up (Incidence Rate Ratio, 0.23; 95% CI, 0.12-0.47; P < 0.001). Belzutifan demonstrated efficacy across VHL-associated lesions, with favorable safety profile. Most adverse events were grade 1-2. A reduction in procedure rate was observed after treatment initiation.

real-world

Belzutifan

VHL disease

HIF-2α

Details

Title: Subtitle: Clinical Outcomes of HIF-2α inhibition in Von Hippel-Lindau Disease: A Multicenter Real-World Study
Creators: Mousab Al Abbas - Mayo Clinic in Arizona
Jabra Zarka - Mayo Clinic
Alvin C Silva - Mayo Clinic Hospital
Filippo Cingolani - Mayo Clinic in Arizona
Muhammed Uzair Sarfraz - Mayo Clinic in Arizona
Albert Jang - Mayo Clinic
Muhammad Ali Khan - Mayo Clinic in Arizona
Fouad Nahhat - Mayo Clinic Hospital
Winston Tan - Mayo Clinic in Florida
Brian A Costello - Mayo Clinic in Arizona
Haidar Abdul-Muhsin - Mayo Clinic Hospital
Irbaz Bin Riaz - Mayo Clinic in Arizona
Yousef Zakharia - Mayo Clinic in Arizona
Resource Type: Journal article
Publication Details: The oncologist (Dayton, Ohio), Vol.31(10), oyag331
DOI: 10.1093/oncolo/oyag331
PMID: 42610708
NLM abbreviation: Oncologist
ISSN: 1083-7159
eISSN: 1549-490X
Publisher: Oxford University Press
Language: English
Electronic publication date: 08/18/2026
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9985219923302771

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