Is Mvasi (bevacizumab) effective for treating hereditary hemorrhagic telangiectasia (HHT) in a patient with iron deficiency anemia and history of epistaxis and gastrointestinal bleeding?

Mvasi (Bevacizumab-awwb) is Highly Effective and Guideline-Recommended for This Patient's Severe HHT

This 57-year-old woman with severe HHT-related GI bleeding and epistaxis meets clear criteria for bevacizumab therapy and should continue treatment with Mvasi, as she has demonstrated a complete clinical response and represents a textbook indication per international HHT guidelines. 1

Disease Severity Classification

This patient has severe HHT-related GI bleeding based on the Second International HHT Guidelines classification system: 1

• Hemoglobin of 7.7 g/dL despite IV iron every 2 weeks (does not meet hemoglobin goals despite adequate iron replacement)
• Required blood transfusions (2 units when hemoglobin dropped to 7.5)
• Daily melena and epistaxis from GI tract, nasal cavity, and pulmonary AVMs
• Failed alternative therapy (pomalidomide discontinued due to side effects)

The guidelines explicitly define severe GI bleeding as patients who do not meet hemoglobin goals despite adequate iron replacement or require blood transfusions—both criteria this patient fulfills. 1

Guideline-Based Recommendation for Bevacizumab

The Second International HHT Guidelines (2021, published in Blood) provide a strong recommendation for IV bevacizumab in moderate to severe HHT-related GI bleeding (Quality of Evidence: moderate, Strength of Recommendation: strong). 1

The guidelines specifically state that clinicians should consider treatment of moderate to severe HHT-related GI bleeding with intravenous bevacizumab or other systemic antiangiogenic therapy. 1

Evidence Supporting This Recommendation

The InHIBIT-Bleed multicenter retrospective study of 238 patients with moderate-to-severe HHT-associated bleeding demonstrated: 1

• Mean hemoglobin improvement of 3.2 g/dL
• 82% reduction in red blood cell transfusions
• 70% reduction in iron infusions
• VTE rate of only 2% with no fatal adverse events

This patient's documented response mirrors these outcomes—she had a complete response on initial therapy and experienced worsening (hemoglobin drop to 7.5, increased epistaxis) when bevacizumab was held for parathyroidectomy. 1

Dosing Protocol Alignment

The current regimen (5 mg/kg IV every 28 days for maintenance) aligns with guideline recommendations: 1

• Induction: 5 mg/kg every 2 weeks for 4-6 doses (already completed)
• Maintenance: 5 mg/kg every 1-3 months (patient is on monthly dosing, which is appropriate)

The guidelines note that maintenance dosing is variable, and 5 mg/kg every 1-3 months is an acceptable option. 1

Required Monitoring

Essential monitoring parameters during bevacizumab therapy include: 1

• Hypertension (most common adverse effect)
• Proteinuria (check urinalysis regularly)
• Infection risk (particularly given history of brain abscess)
• Delayed wound healing (relevant given recent parathyroidectomy)
• Venous thromboembolism (2% incidence in InHIBIT-Bleed study)

Critical Pitfall: Treatment Interruption

This case demonstrates a critical pitfall—interrupting bevacizumab therapy leads to rapid disease recurrence. When treatment was held for 2 doses perioperatively, the patient experienced: [@case details]

• Worsening nosebleeds
• Hemoglobin drop to 7.5 g/dL
• Required 2 doses of IV iron
• Needed blood transfusions

This underscores that bevacizumab provides disease control rather than cure, and maintenance therapy is essential. The guidelines acknowledge that risks of long-term maintenance therapy are unknown but support continued use in responders. [@2@, @8@]

Biosimilar Equivalence

Mvasi (bevacizumab-awwb) is an FDA-approved biosimilar to Avastin with demonstrated equivalent efficacy and safety. [@case details] The HHT guidelines reference bevacizumab generically, and biosimilars are appropriate substitutes for the reference product in this indication.

Insurance Appeal Justification

While the insurer labels HHT as "experimental, investigational, or unproven," this contradicts: 1

• Strong recommendation from Second International HHT Guidelines (2021, Blood)
• Moderate quality of evidence supporting use
• 238-patient multicenter study (InHIBIT-Bleed) demonstrating efficacy
• Patient's documented complete response to therapy
• Clinical deterioration when therapy interrupted

The EASL Clinical Practice Guidelines (2016, Journal of Hepatology) also support bevacizumab use in HHT with liver vascular malformations, noting complete response in 12% and partial response in 70% of patients. 1

Concurrent Iron Management

Continue aggressive IV iron replacement (INFeD 500 mg every 2-4 weeks as tolerated) alongside bevacizumab, as the guidelines note these therapies can be coadministered. 1 The patient's inability to tolerate monoferric and limited response to Venofer makes INFeD the appropriate choice despite requiring slower infusion rates.