Abstract Number: OC 59.1
Meeting: ISTH 2021 Congress
Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic and bleeding disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT.
Aims: To evaluate the safety and effectiveness of low-dose oral pazopanib for severe HHT-associated bleeding.
Methods: We analyzed outcomes of HHT patients with severe bleeding and transfusion dependence treated on a predefined institutional pazopanib treatment pathway for ≥12 months. The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation.
Results: Patients and Treatment. 13 transfusion-dependent HHT patients with severe epistaxis and/or gastrointestinal bleeding received pazopanib [median (range) dose 100 (25-300) mg daily)] for a median of 22 months. Patient median (range) age was 66 (53-78) years and 46% were female.
Effectiveness. All patients achieved RBC transfusion independence (≥3 months transfusion-free, FIGURE 1). Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P<0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P<0.0001) after 12 months of treatment. Compared with 3 months pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P<0.0001) and elemental iron infused decreased by 92% (median of 4500 vs. 0 milligrams, P=0.005) during the first 3 months of treatment; improvements were maintained over time. Local hemostatic procedures dropped 90%. Effectiveness outcomes are summarized in FIGURE 2.
Safety. Pazopanib was well-tolerated: hypertension (31%), lymphocytopenia (23%), and fatigue (23%) were the most common adverse events (none serious). No patient developed thromboembolism.
Conclusions: 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.
To cite this abstract in AMA style:Parambil J, Gossage J, McCrae K, Woodard T, Menon KN, Timmerman K, Pederson D, Sprecher D, Al-Samkari H. Oral Pazopanib Results in Durable Hemostasis in Patients with Severe Bleeding and RBC Transfusion-dependent Hereditary Hemorrhagic Telangiectasia [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/oral-pazopanib-results-in-durable-hemostasis-in-patients-with-severe-bleeding-and-rbc-transfusion-dependent-hereditary-hemorrhagic-telangiectasia/. Accessed December 3, 2021.
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