High importance
Sep 23, 2026
To profile circulating angiogenic and inflammatory biomarkers in patients with hereditary hemorrhagic telangiectasia (HHT) undergoing bevacizumab treatment and assess their relation to clinical severity and response to therapy.
An exploratory, observational, prospective study involving nine bevacizumab-treated HHT patients matched with controls. Blood samples were collected before and during treatment to analyze 22 biomarkers.
VEGF-A levels increased significantly during bevacizumab treatment, indicating it cannot serve as a monitoring biomarker. PDGF and TSP1 levels were elevated in treatment responders, while discrepancies in biomarker levels between HHT patients and controls were noted, with certain biomarkers downregulated and others, like IL-6, elevated. Several biomarkers positively correlated with anemia severity (hemoglobin levels).
The study had a small sample size (only nine patients), and findings need validation in larger cohorts to establish robustness. The use of only selected biomarkers may limit comprehensive assessment.
Identifying reliable biomarkers can enhance monitoring strategies for anti-angiogenic therapies like bevacizumab in HHT, which is crucial for improving patient management and treatment outcomes.
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder affecting BMP9-ALK1-endoglin signaling, leading to vascular malformations. HHT is marked by recurrent bleeding (mostly epistaxis and gastrointestinal) that can result in severe anemia. Thus, there is a need for circulating biomarkers to quantify clinical severity, monitor response to anti-angiogenic therapies such as bevacizumab and to support diagnosis. MATERIALS AND METHODS: This is an exploratory, observational, prospective study conducted in an HHT referral Unit. We profiled 22 circulating angiogenic and inflammatory biomarkers in nine bevacizumab-treated HHT patients, 1:1 matched with HHT controls and healthy controls. HHT patients with indication for bevacizumab treatment underwent blood sampling before and during treatment. The main objective is to describe the evolution of these biomarkers during bevacizumab treatment. Secondary objectives were to identify (i) biomarkers associated with HHT diagnosis, and (ii) biomarkers that scale with anemia severity using hemoglobin (Hb). RESULTS: Circulating VEGF-A increased markedly during bevacizumab treatment, precluding its use as a monitoring biomarker. PDGF, TSP1, sVEGFR1, FGF2, VEGFc, and PLGF significantly change from baseline in responders, with PDGF and TSP1 showing significantly higher end-of-treatment levels compared to non-responders. Comparing HHT patients to non-HHT controls at baseline, BMP9, sENG, sVEGFR1, sVEGFR2, VEGFc, TSP1, TSP2, and PDGF levels were significantly downregulated, whereas IL-6 was increased. Finally, VEGFc, sVEGFR1, and TSP1 positively correlated with Hb levels. CONCLUSIONS: These data identify candidate circulating biomarkers for monitoring bevacizumab response and quantifying HHT disease burden. Further studies are needed to validate these findings.