Innovative solutions? Belzutifan therapy for hemangioblastomas in Von Hippel-Lindau disease: A systematic review and...

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant disorder that predisposes patients to develop multiple cysts and tumors, such as hemangioblastomas (HBs) and clear cell renal cell carcinoma (ccRCC), due to mutations in the VHL tumor suppressor gene. While treatment of HBs varies based on their characteristics and has improved patient survival, it still involves high morbidity and mortality, leading to ongoing debates and studies to refine therapy strategies. Recent developments include the emergence of Belzutifan, a novel inhibitor targeting hypoxia-inducible factor 2α (HIF-2α), which has shown promising results in ongoing trials, particularly for patients not immediately requiring surgery.

This systematic review and meta-analysis aimed to comprehensively evaluate the efficacy and safety of Belzutifan for treating HBs associated with VHL disease. Search was conducted across Medline, Embase, Cochrane, and Web of Science databases. Statistical Analysis was performed, with proportions and 95 % confidence intervals. Statistical analyses were carried out using R Studio.

Ten studies were selected, comprising 553 patients. The population mean age was 40 (24-65), and 50 % of the population was formed by males. In terms of proportion, 6 analyses were performed: Disease Stability of 31 % [95 %CI:14 %-47 %; I2 = 2 %]; Disease Progression of 2 %[95 %CI:0 %-9 %; I2 = 0 %]; Partial Response of 75 % [95 %CI:54 %-96 %; I2 = 58 %]. Complete response of 1 % [95 %CI:0 %-7 %; I2 = 0 %];and Side effects, anemia 81 % rate [95 % CI:54 %-100 %; I2 = 94 %], and fatigue rate of 79 % [95 % CI:54 %-100 %;I2 = 94 %].

Results indicate that Belzutifan effectively stabilizes disease, reduces tumor progression, and achieves significant therapeutic responses, although side effects like anemia and fatigue were noted.