Oral Pazopanib Results in Durable Hemostasis in Patients with Severe Bleeding and RBC Transfusion-dependent Hereditary Hemorrhagic Telangiectasia

Hanny Al-Samkari, M.D.
Massachusetts General Hospital
Boston, Massachusetts, U.S.

On Tuesday, July 20, 2021, Hanny Al-Samkari, M.D., of Massachusetts General Hospital in Boston presented results on oral pazopanib for severe hereditary hemorrhagic telangiectasia (HHT)-associated bleeding. HHT, also known as Osler‐Weber‐Rendu syndrome, is a relatively common (1 in 5,000 persons), 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. Despite the significant morbidity and mortality from this bleeding disorder, it has no U.S. FDA– or EMA-approved therapies. Pazopanib is an oral multikinase angiogenesis inhibitor with promise to treat bleeding in HHT.

The aim of this study was to evaluate the safety and efficacy of low-dose oral pazopanib for patients with severe HHT-associated bleeding. A total of 13 patients were researched for a median of 22 months. All 13 patients had RBC transfusion dependence as defined by the Gale criteria (two or more units of RBCs transfused monthly for a duration of three months or longer), although most patients required significantly more than the minimum to meet this definition (the median number of RBC units transfused in the three months prior to pazopanib initiation was 16). Al-Samkari commented that on pazopanib, all patients achieved RBC transfusion independence, defined as freedom from RBC transfusion for three or more months, within the first six months of pazopanib treatment. Concurrently with this, pazopanib increased mean hemoglobin by 4.8 g/dL (and decreased mean epistaxis severity score by 4.77 points) after 12 months of treatment. Compared with three months pretreatment, RBC transfusions decreased by 93% and elemental iron infused decreased by 92% during the first three months of treatment, with these improvements being maintained over time. The safety profile of pazopanib was well tolerated from this study as well, with hypertension (31%), lymphocytopenia (23%), and fatigue (23%) being the most common adverse events reported. The median dose achieving these outcomes was just 100 mg daily, which is one-eighth the starting dose of pazopanib used to treat malignancies (800 mg daily).

Al-Samkari concluded that low-dose oral pazopanib was safe and effective to manage severe bleeding in HHT, durably liberating all patients from transfusion dependence and normalizing hematologic parameters at doses much lower than used to treat malignancies, and that prospective randomized trials were coming to confirm these promising findings.