An International Multicenter Study of Bevacizumab for Bleeding in Hereditary Hemorrhagic Telangiectasia (the InHIBIT-Bleed Study)

On Sunday, Hanny Al-Samkari, M.D., of Massachusetts General Hospital in Boston, MA, presented results on systemic bevacizumab for bleeding in hereditary hemorrhagic telangiectasia (HHT) from the InHIBIT-Bleed Study. HHT, also known as Osler‐Weber‐Rendu syndrome, is a relatively common, under‐recognized autosomal‐dominant disorder that results in multisystem disordered angiogenesis and is characterized by telangiectasias and arteriovenous malformations of skin, mucosa, and viscera, causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab is a humanized anti-VEGF monoclonal IgG1 antibody that has been found to be effective in combination with chemotherapy to treat advanced colorectal cancer, advanced non-small cell lung cancer, metastatic breast cancer, and advanced renal cell cancer. It is believed that this anti-vascular endothelial growth factor antibody may be effective to treat bleeding in HHT.

The aim of this multicenter study was to evaluate the safety and efficacy of systemic bevacizumab in patients with HHT-associated bleeding. A total of 238 patients were treated with bevacizumab for a median of 1 year. What did Al-Samkari and team discover? Bevacizumab increased mean hemoglobin by 3.2 g/dL and decreased the epistaxis severity score by 3.4 points (a 50% reduction) during the first year of treatment. Compared with 6 months pretreatment, both the number of red blood cell units transfused and iron infusions decreased precipitously during the first 6 months of bevacizumab treatment. Following the initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower Epistaxis Severity Score than intermittent/as-needed maintenance but with more drug exposure. Bevacizumab was well tolerated, with 340 patient-years of treatment evaluable for adverse events, with hypertension, fatigue, proteinuria, and myalgia/arthralgia being the most commonly reported.

Al-Samkari remarked that systemic bevacizumab was safe and highly effective in managing chronic bleeding and anemia in HHT. Prior to the introduction of the InHIBIT-Bleed Study, data evaluating bevacizumab were sparse and limited to case studies and small single-center case series.