Page 133 - 2021_06-Haematologica-web

Hemostasis
An international, multicenter study of intravenous bevacizumab for bleeding
in hereditary hemorrhagic telangiectasia: the InHIBIT-Bleed study
Ferrata Storti Foundation
Haematologica 2021 Volume 106(8):2161-2169
Hanny Al-Samkari,1,2 Raj S. Kasthuri,3 Joseph G. Parambil,4 Hasan A. Albitar,5 Yahya A. Almodallal,6 Carolina Vázquez,7 Marcelo M. Serra,7 Sophie Dupuis- Girod,8 Craig B. Wilsen,9 Justin P. McWilliams,9 Evan H. Fountain,10 James R. Gossage,10 Clifford R. Weiss,11 Muhammad A. Latif,11 Assaf Issachar,12 Meir Mei-Zahav,12 Mary E. Meek,13 Miles Conrad,14 Josanna Rodriguez-Lopez,1,15 David J. Kuter1,2 and Vivek N. Iyer16
1Harvard Medical School, Boston, MA, USA; 2Division of Hematology, Massachusetts General Hospital, Boston, MA, USA; 3Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA; 5Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; 6Department of Pediatrics, Mayo Clinic, Rochester, MN, USA; 7HHT Center Argentina, Department of Internal Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 8Centre de Référence pour la Maladie de Rendu-Osler, Hospices Civils de Lyon, Lyon, France; 9Division of Interventional Radiology, Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 10Division of Pulmonary, Critical Care, and Sleep Medicine, Augusta University, Augusta, GA, USA; 11Russel H. Morgan Department of Radiology and Radiological Science, Division of Interventional Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 12Schneider Children’s Medical Center of Israel, Tel Aviv University, Tel Aviv, Israel; 13Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 14Department of Radiology, University of California San Francisco Medical Center, San Francisco, CA, USA; 15Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA and 16Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
ABSTRACT
Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder that causes chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retro- spective study evaluated the use of systemic bevacizumab to treat HHT- associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, Epistaxis Severity Score (ESS), red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. Bevacizumab was given to 238 HHT patients for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% confidence interval: 2.9-3.5 g/dL); i.e., from a mean hemoglobin of 8.6 (8.5- 8.8) g/dL to 11.8 (11.5-12.1) g/dL; P<0.0001) and decreased the 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. Compared with 6 months before treatment, the number of red blood cell units transfused decreased by 82% (median of 6.0 [interquartile range, 0.0-13.0] units versus 0 [0.0-1.0] units; P<0.0001) and iron infusions decreased by 70% (median of 6.0 [1.0-18.0] infusions versus 1.0 [0.0-4.0] infusions, P<0.0001) during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of the 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: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective for managing chronic bleeding and anemia in HHT.
Correspondence:
HANNY AL-SAMKARI
hal-samkari@mgh.harvard.edu
Received: June 4 2020. Accepted: June 30, 2020. Pre-published: July 16, 2020.
https://doi.org/10.3324/haematol.2020.261859
©2021 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2021; 106(8)
2161
ARTICLE