What are appropriate therapeutic alternatives to Papzimeos (zopapogene imadenovec) for treating adults with recurrent respiratory papillomatosis?

Therapeutic Alternatives to Papzimeos for Adult Recurrent Respiratory Papillomatosis

Surgical removal using contemporary laryngeal instruments, including laser and microdebrider, combined with adjuvant therapy such as intralesional or systemic bevacizumab is the most appropriate therapeutic alternative to Papzimeos for adults with recurrent respiratory papillomatosis. 1

Primary Treatment Options

Surgical Interventions

• Surgical excision: Remains the standard of care for managing RRP
  • Contemporary laryngeal instruments including laser and microdebrider are recommended to prevent airway obstruction and reduce dysphonia 1
  • Important to avoid injury to underlying vibratory layers of vocal folds to prevent long-term dysphonia related to scar formation
  • Surgical approaches include:
    • Laser ablation
    • Microdebrider excision
    • Cold steel excision

Adjuvant Pharmacologic Options

Bevacizumab

• Systemic administration:

  • Highly effective in severe RRP cases with 95% of patients experiencing prolonged surgical intervals 2
  • More than half of patients treated systemically don't require additional surgical interventions during follow-up (mean 21.6 months) 2
  • Initial dosing: 15 mg/kg at 3-week intervals, then individually titrated down 3
  • Side effects include hypertension, headache, elevated creatinine, and epistaxis 3

• Intralesional administration:

  • Moderately effective with 62% of patients experiencing extended surgical intervals 2
  • Less effective than systemic administration but may have fewer systemic side effects

Cidofovir (Intralesional)

• Mean concentration: 7.5 mg/ml per injection
• Average of 6 injections per patient with 26 days between injections
• Complete response rates:
  • Adult-onset RRP: 74%
  • Juvenile-onset RRP: 56.5% 4
• Low risk of laryngeal dysplasia (1.48%) 4

Safety Considerations

Procedural Safety

• Protective eyewear required for both patient and laser team
• Maintain inspired oxygen concentration below 40% to minimize ignition risk 1
• Continuous suction to remove smoke containing potential viral particles
• Use tight-fitting masks with small pore sizes and dedicated smoke evacuators 1

Preventive Measures

• HPV vaccination strongly recommended for patients with RRP aged 9-26 years
  • Quadrivalent or nonavalent vaccine preferred due to RRP's relationship to HPV types 6 and 11 1
  • May help prolong time to recurrence 5

Treatment Algorithm

1. Initial Assessment:

   • Evaluate disease severity (extent, airway involvement, frequency of recurrence)
   • Assess for tracheobronchial involvement

2. Primary Treatment:

   • Surgical excision using laser or microdebrider for all patients with symptomatic disease

3. For Severe/Recurrent Disease:

   • Add adjuvant therapy based on severity:
     • For moderate disease: Consider intralesional cidofovir
     • For severe disease (high burden, frequent recurrence, tracheobronchial involvement): Consider systemic bevacizumab

4. Monitoring and Follow-up:

   • Regular endoscopic evaluation based on disease aggressiveness
   • Adjust treatment intervals based on clinical response

Important Caveats

• RRP is rarely curative with surgery alone since HPV is present in adjacent normal-appearing mucosa 1
• The clinical course is unpredictable and may require lifelong management 4
• Bevacizumab should be used cautiously in patients with hypertension, bleeding disorders, or autoimmune conditions 3
• Consider HPV vaccination for all eligible patients with RRP as it may help reduce recurrence rates 5