Systemic bevacizumab for high-output cardiac failure in hereditary hemorrhagic telangiectasia: an international survey of HHT centers

Orphanet J Rare Dis. 2019 Nov 14;14(1):256. doi: 10.1186/s13023-019-1239-6.

Abstract

Background: Systemic bevacizumab is a novel targeted anti-angiogenic therapy for high-output cardiac failure (HOCF) in hereditary hemorrhagic telangiectasia (HHT) but published data is limited. This survey-based study measured physician-reported safety, effectiveness and current treatment practices for systemic bevacizumab in HHT-HOCF.

Methods: A 27-item survey was sent to center directors of 31 international HHT Centers of Excellence.

Results: Response rate was 74% with centers reporting 150 total patients receiving systemic bevacizumab for HHT-HOCF. Approximately two-thirds of centers had treated ≥5 patients. All centers utilize a 5 mg/kg dose for induction treatment and most administer 6 doses (range, 4-6) every 2 weeks, although maintenance regimens varied considerably. Center directors reported bevacizumab to be effective, with 55% reporting significant improvement in cardiac index and HOCF symptoms in most patients treated with bevacizumab, although normalization of cardiac parameters was uncommon. Adverse events were uncommon with three-quarters of centers reporting adverse event rates < 10%. Discontinuation for adverse events or ineffectiveness was rare. Bevacizumab was typically administered by hematologists and pulmonologists (50 and 39% of centers, respectively), with highly variable thresholds for initiation. Although half the centers reported difficulty with the insurance approval process, 70% of centers were ultimately able to obtain coverage for most or all of their patients.

Conclusions: Systemic bevacizumab is a widely-used therapy for HHT-HOCF with reasonable safety and effectiveness. HHT centers appear to vary considerably in maintenance treatment practices and disease severity thresholds for initiation of bevacizumab in HHT-related HOCF.

Keywords: Arteriovenous malformation; Bevacizumab; HHT; Heart failure; Hereditary hemorrhagic telangiectasia; High-output cardiac failure; Osler-weber-Rendu.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / etiology*
  • Humans
  • Male
  • Middle Aged
  • Surveys and Questionnaires
  • Telangiectasia, Hereditary Hemorrhagic / complications*
  • Telangiectasia, Hereditary Hemorrhagic / drug therapy*
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • Bevacizumab