Correspondence

More on Bevacizumab in Hereditary Hemorrhagic Telangiectasia

N Engl J Med 2009; 361:931-932August 27, 2009

Article

To the Editor:

Bose et al. (May 14 issue)1 report on a patient with hereditary hemorrhagic telangiectasia (HHT) who was treated with bevacizumab for epistaxis. Our patient was a 55-year-old man with HHT (endoglin mutation P.LYS402.FS) with intractable pain and frequent episodes of pancreatitis related to pancreatic arteriovenous malformations. Surgery and embolization were not feasible. An indium-111–labeled bevacizumab single-photon-emission computed tomographic (CT) scan2 showed elevated tracer uptake in the arteriovenous malformations. Bevacizumab at a dose of 5.0 mg per kilogram of body weight every 2 weeks was started 1 year ago. This treatment immediately stopped the epistaxis, the skin vascular signs became less pronounced, and the frequency and severity of pancreatitis diminished. After 5 months, the dose was increased to 7.5 mg per kilogram every 2 weeks. Thereafter, morphine and tube feeding could be discontinued, and the patient resumed work. No change in the volume of the arteriovenous malformations was observed on CT. The patient still receives bevacizumab.

Sjoukje Oosting, M.D.
Wouter Nagengast, M.D.
Elisabeth de Vries, M.D., Ph.D.
University Medical Center Groningen, Groningen, the Netherlands
s.oosting@int.umcg.nl

Dr. de Vries reports attending an advisory board meeting for Roche in May 2009 for which the University Medical Center Groningen received €2,000 ($2,838). No other potential conflict of interest relevant to this letter was reported.

2 References

1. 1

   Bose P, Holter JL, Selby GB. Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 2009;360:2143-2144
   Full Text | Web of Science | Medline

2. 2

   Nagengast WB, de Vries EG, Hospers GA, et al. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med 2007;48:1313-1319
   CrossRef | Web of Science | Medline

To the Editor:

We administered bevacizumab to a 65-year-old woman with HHT and life-threatening, recurrent hemorrhage. She had undergone liver transplantation 10 years earlier for arteriovenous shunting. Over a 1-year period, worsening anemia developed because of recurrent epistaxis and gastrointestinal bleeding, despite maximal standard therapy of iron infusions, estrogens, and tranexamic acid. From February through July 2008, she received 27 transfusions containing a total of 52 packed cells. Six courses of bevacizumab (5 mg per kilogram) were administered without any adverse events. Blood transfusions were not required for 2 months. Only medical therapy was continued. In December 2008, hemorrhage resumed, but with a reduced need for blood transfusion, as compared with her earlier course.

Frederique Retornaz, M.D., Ph.D.
Yves Rinaldi, M.D.
Hôpital Ambroise Paré, Marseille, France
fretornaz@cgd13.fr

Christophe Duvoux, M.D.
Hôpital Henri-Mondor, Créteil, France

Author/Editor Response

The cases described by Oosting et al. and Retornaz et al. give further evidence of the efficacy of bevacizumab in patients with HHT. Both cases also show that symptoms and transfusion requirements improve with this therapy, without an appreciable change in arteriovenous malformations. Like Oosting et al., we found no difference in the size of our patient's pulmonary arteriovenous malformations on CT before and after bevacizumab. Their experience demonstrates the long-term safety and tolerability of bevacizumab in such patients. Our patient continues to report symptomatic benefit more than a year after completing therapy, and he has required only one intravenous infusion of iron during this time. His hemoglobin levels have remained stable at 14 to 15 g per deciliter. The cost of our patient's regimen (a total of 30 mg per kilogram over four cycles) would be approximately $12,000 today. The costs of continuing the drug in the long term, especially without a Food and Drug Administration–approved indication, would be prohibitive. Our case shows that intermittent dosing allows for long-term, symptomatic improvement and stability of pulmonary arteriovenous malformations.

Prithviraj Bose, M.D.
Jennifer L. Holter, M.D.
George B. Selby, M.D.
University of Oklahoma Health Sciences Center, Oklahoma City, OK
prithviraj-bose@ouhsc.edu

Citing Articles (4)

Citing Articles

1. 1

   C. Rohrmeier, H. G. Sachs, T. S. Kuehnel. (2012) A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia. European Archives of Oto-Rhino-Laryngology 269:2, 531-536
   CrossRef

2. 2

   Georgia Lazaraki, Evangelos Akriviadis, Ioannis Pilpilidis, Ioanna Parisi, Dimitrios Tzilves, Anestis Tarpangos. (2011) Low Dose of Bevacizumab Is Safe and Effective in Preventing Bleeding Episodes in Hereditary Hemorrhagic Telangiectasia. The American Journal of Gastroenterology 106:12, 2204-2206
   CrossRef

3. 3

   Erik Storkebaum, Annelies Quaegebeur, Miikka Vikkula, Peter Carmeliet. (2011) Cerebrovascular disorders: molecular insights and therapeutic opportunities. Nature Neuroscience 14:11, 1390-1397
   CrossRef

4. 4

   Brinkerhoff, Brian T., Poetker, David M., Choong, Nicholas W., . (2011) Long-Term Therapy with Bevacizumab in Hereditary Hemorrhagic Telangiectasia. New England Journal of Medicine 364:7, 688-689
   Full Text