Introduction: The use of MK-6482 (Belzutifan) may completely change the treatment of VHL patient with ccRCC, potentially reducing unnecessary surgeries along with the consequent renal functional impairment. Since no data about the generalizability of the study to real-world VHL patients is available, the aim of the study is to investigate this topic relying on a prospective database of VHL patients enrolled in multidisciplinary surveillance program. Methods: Since January 2021, a multidisciplinary program devoted to VHL disease is operational at our institution. All the consenting patients with VHL diagnosis based on pathogenic variant are enrolled into a prospective, observational surveillance study. In our outpatient clinic, each patient receives diagnostic and clinical evaluation by a multidisciplinary team of physicians to cover all the potential areas of interest in VHL disease. The primary outcome was the overall inclusion rate and the inclusion/exclusion criterion-specific rate of patients that would have access to the MK-6482-004 trial. Inclusion criteria were: 1) diagnosis of VHL pathogenic variant; 2) at least one measurable RCC =10 mm in diameter; 3) Eastern Cooperative Oncology Group performance-status [ECOG-PS] score of 0 or 1. Exclusion criteria were: 1) RCC requiring immediate surgery and 2) metastatic disease. Results: Overall, 30 patients were enrolled in our VHL program. The median (IQR) age was 48 (27-62) and the median eGFR was 92 mL/min/1.73m2. The rate of real-world VHL patient that would have been included in the trial was 23% (n=7) only. Specifically, 40% (n=12) of the patients are excluded owing to absence of any measurable renal cell carcinoma =10 mm in diameter. 37% (n=11) of the patients are excluded owing to ECOG-PS higher than 1. 7% (n=2) patient would have been excluded due to evidence of metastatic disease. Difference in descriptive statistics of baseline characteristics between MK-6482-004 patients and real-world patients are summarized in Fig. 1. Conclusions: Despite the ramping enthusiasm generated by the MK-6482-004 trial, the findings of the study appear applicable to a small proportion of real world VHL patients. Larger studies, focusing also on extra-renal VHL lesions are required to better define the role of MK-6482 (Belzutifan) for the treatment of VHL patients. SOURCE OF Funding: Supported by VHL Alliance
