Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia

• Published in: Orphanet journal of rare diseases 2019-02, Vol.14 (1), p.28-14, Article 28
• Main Authors: Buscarini, Elisabetta, Botella, Luisa Maria, Geisthoff, Urban, Kjeldsen, Anette D, Mager, Hans Jurgen, Pagella, Fabio, Suppressa, Patrizia, Zarrabeitia, Roberto, Dupuis-Girod, Sophie, Shovlin, Claire L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adverse event; Anemia; Angiogenesis; Angiogenesis inhibitors; Antineoplastic agents; Arteriovenous malformation; Arteriovenous malformations; Bevacizumab; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Bleeding; Cancer therapies; Cardiovascular diseases; Colorectal cancer; Dosage and administration; Drowsiness; Drug therapy; Drugs; Dysplasia; Epistaxis - drug therapy; Epistaxis - metabolism; Epistaxis - physiopathology; Female; Gastrointestinal hemorrhage; Headache; Heart failure; Hemorrhage; Hemorrhage - drug therapy; Hemorrhage - metabolism; Hemorrhage - physiopathology; Hereditary hemorrhagic telangiectasia; Humans; Immunotherapy; Ischemia; Liver; Male; Males; Medical research; Metastasis; Monoclonal antibodies; Mortality; Multiple myeloma; Nosebleed; Patients; Peripheral neuropathy; Prevention; Proteinuria; Pulmonary arteries; Rare diseases; Retrospective Studies; Safety and security measures; Surveys and Questionnaires; Targeted cancer therapy; Telangiectasia, Hereditary Hemorrhagic - drug therapy; Telangiectasia, Hereditary Hemorrhagic - metabolism; Telangiectasia, Hereditary Hemorrhagic - physiopathology; Telangiectasis; Terminology; Terms and phrases; Thalidomide; Thalidomide - adverse effects; Thalidomide - therapeutic use; Toxicity; Tranexamic acid; Transplants & implants; Vascular diseases; Vascular endothelial growth factor; Young Adult
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-018-0982-4

Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular dysplasia that leads to nosebleeds and visceral arteriovenous malformations (AVMs). Anti-angiogenic drugs thalidomide and bevacizumab have been increasingly used off-label with variable results. The HHT working group within the ERN for Rare Multisystemic Vascular Diseases (VASCERN), developed a questionnaire-based retrospective capture of adverse events (AEs) classified using the Common Terminology Criteria for Adverse Events. Sixty-nine HHT patients received bevacizumab, 37 (50.6%) for high output cardiac failure/hepatic AVMs, and 32 (49.4%) for bleeding; the 69 patients received bevacizumab for a mean of 11 months for a total of 63.8 person/years treatment. 67 received thalidomide, all for epistaxis and/or gastrointestinal bleeding; they received thalidomide for a mean of 13.4 months/patient for a total of 75 person/years treatment. AEs were reported in 58 patients, 33 with bevacizumab, 37 with thalidomide. 32 grade 1-3 AEs related to bevacizumab were reported with an average incidence rate of 50 per 100 person-years. 34 grade 1-3 AEs related to thalidomide were reported with an average incidence rate of 45.3 per 100 person-years. Bevacizumab AEs were more common in females (27 AEs in 46 women) than males (6 in 23, p