Abstract Number: OC 09.2
Meeting: ISTH 2020 Congress
Background: Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare bleeding disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. Current data evaluating this is limited to small single-center case series.
Aims: Evaluate safety and effectiveness of systemic bevacizumab to treat HHT-associated bleeding in a large, multicenter, international study.
Methods: Multicenter retrospective study of HHT patients receiving bevacizumab at 12 international HHT treatment centers, comparing hemoglobin, epistaxis severity score (a well-validated 10-point bleeding score in HHT), RBC transfusions, and iron infusions before and after bevacizumab treatment.
Results: 238 patients were treated with bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5-8.8) g/dL versus 11.8 (11.5-12.1) g/dL, p< 0.0001)] and decreased the epistaxis severity score (ESS) by 3.4 (3.2-3.7) points [mean ESS 6.8 (6.6-7.1) versus 3.4 (3.2-3.7), P< 0.0001] during the first year of treatment, FIGURE 1A-B. Compared with 6 months pretreatment, RBC units transfused decreased by 82% [median of 9.0 (IQR 5.0-16.0) units versus 0 (IQR, 0.0-2.0) units, P< 0.0001] and iron infusions decreased by 70% [median of 8.0 (3.0-20.0) infusions versus 2.0 (0.0-5.0) infusions, P< 0.0001] during the first 6 months of bevacizumab treatment, FIGURE 1C-D. Outcomes were similar regardless of underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as needed maintenance but with more drug exposure. Bevacizumab was well tolerated, with 343 patient-years of treatment evaluable for adverse events; hypertension, fatigue, proteinuria, and myalgia/arthralgia were most common (TABLE) and 5% of patients discontinued treatment due to side-effects.
Conclusions: In a large. multicenter, international study, systemic bevacizumab was safe and highly effective to manage chronic bleeding and anemia in HHT.
|Treatment-Emergent Adverse Event||Number of Patients (%)||Treatment-Emergent Adverse Event||Number of Patients (%)|
|Hypertension (new-onset or worse from baseline)||41 (18%)*||Rash||3 (1%)|
|Fatigue||23 (10%)||Abdominal pain/gastrointestinal upset||3 (1%)|
|Proteinuria||21 (9%)||Lightheadedness||2 (1%)|
|Myalgia and/or arthralgia||14 (6%)||Dyspnea||2 (1%)|
|Headache||9 (4%)||Hoarseness||2 (1%)|
|Venous thromboembolism||5 (2%)||Bone marrow suppression||2 (1%)|
|Transaminase/alkaline phosphatase elevation||3 (1%)||Other**||7 (3%)|
|*26 patients with new-onset hypertension and 15 patients with hypertension worsened from baseline.|
|**Includes one report each of lower extremity edema, worsened epistaxis, diarrhea, lower extremity venous ulceration, poor wound healing, non-cardioembolic stroke, and Staphylococcus aureus skin infection.|
[TABLE. Treatment-emergent adverse events (TEAEs) identified by treating clinician as likely or possibly due to bevacizumab.]
To cite this abstract in AMA style:Al-Samkari H, Kasthuri R, Parambil J, Albitar H, Almodallal Y, Vazquez C, Serra M, Dupuis-Girod S, Wilsen C, McWilliams J, Fountain E, Gossage J, Weiss C, Latif M, Issachar A, Mei-Zahav M, Meek M, Conrad M, Kuter D, Iyer V. An International Multicenter Study of Bevacizumab for Bleeding in Hereditary Hemorrhagic Telangiectasia (The InHIBIT-Bleed Study) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/an-international-multicenter-study-of-bevacizumab-for-bleeding-in-hereditary-hemorrhagic-telangiectasia-the-inhibit-bleed-study/. Accessed September 19, 2020.
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