Assessment of hemoglobin and erythropoietin levels in patients with von Hippel-Lindau syndrome undergoing belzutifan treatment

von Hippel-Lindau (VHL) syndrome is caused by pathogenic germline variants in the VHL gene, predisposing individuals to retinal and CNS angiomas, renal cancer, neuroendocrine tumors, and other neoplasms. Recently, the HIF2A inhibitor Belzutifan has shown efficacy in treating all tumors associated with VHL. A real-world clinical study on the use of Belzutifan in VHL was recently approved by the institutional ethics committee, and 35 VHL patients with different tumors have been included since October 2023. This subproject aims to assess the main adverse effects of the drug, such as anemia, fatigue, and others. To this end, we have collected baseline (pre-treatment) variables from laboratory tests, such as complete blood counts and plasma erythropoietin (EPO) levels, and we will followed the results monthly for up to 6 months of treatment. Preliminary results indicate that all participants developed grade 1-2 anemia, with fatigue and headache being the primary adverse effects (grade 1-2). In five participants with symptomatic anemia or a significant hemoglobin drop in the first 2 months of treatment, subcutaneous (SC) EPO was supplemented efficiently, with prompt recovery. In conclusion, although guidelines for EPO supplementation are not yet defined, we observed that an initial dose of 4,000 IU per week SC was effective for prompt recovery of acute symptoms and improvement of hemoglobin levels in all cases. Maintenance EPO supplementation is still under discussion in our cohort.

Corresponding author: Jose Claudio Casali da Rocha (e-mail: casali.rocha@accamargo.org.br).