What is the role of acyclovir in multiple myeloma patients?

Role of Acyclovir in Multiple Myeloma Patients

Acyclovir or valacyclovir prophylaxis is strongly recommended for all multiple myeloma patients receiving proteasome inhibitors (bortezomib, carfilzomib) or anti-CD38 antibodies (daratumumab) to prevent varicella zoster virus reactivation. 1

Risk of Varicella Zoster Virus (VZV) Reactivation in Multiple Myeloma

• Multiple myeloma patients have a significantly higher risk of VZV reactivation compared to the general population (hazard ratio of 14.8) 1
• Specific treatments that increase VZV reactivation risk include:
  • Proteasome inhibitors (bortezomib, carfilzomib) 1
  • Anti-CD38 antibodies (daratumumab) 1
  • High-dose melphalan followed by autologous stem cell transplantation 1
  • High doses of glucocorticosteroids 1

Antiviral Prophylaxis Recommendations

Indications for Prophylaxis

• Prophylaxis should be initiated for all multiple myeloma patients receiving:
  • Proteasome inhibitors (bortezomib, carfilzomib) 1
  • Anti-CD38 antibodies 1
  • Autologous stem cell transplantation 1, 2
  • High-dose corticosteroids 1

Recommended Agents and Dosing

• Acyclovir 400 mg once or twice daily is effective and sufficient for VZV prophylaxis 3, 4
• Valacyclovir 500 mg daily is an effective alternative 5
• Both medications are well-tolerated with minimal adverse effects 5, 4

Duration of Prophylaxis

• Antiviral prophylaxis should be continued throughout the entire duration of treatment with proteasome inhibitors 6, 3
• Prophylaxis should be extended for at least 6 weeks after discontinuation of proteasome inhibitor therapy 1
• For patients receiving autologous stem cell transplantation, prophylaxis should be continued for 6-12 months post-transplant 2

Efficacy of Antiviral Prophylaxis

• Multiple retrospective studies have demonstrated the high efficacy of antiviral prophylaxis:
  • No VZV reactivation observed in 19 patients receiving 500 mg daily valacyclovir during bortezomib treatment 5
  • No VZV reactivation in 87 patients receiving acyclovir 400 mg daily or 400 mg three times daily during bortezomib treatment 3
  • No VZV reactivation in 100 patients receiving acyclovir 400 mg twice daily during bortezomib-based therapies 7
  • Complete prevention of VZV reactivation in multiple myeloma patients receiving bortezomib with daily acyclovir prophylaxis over 80 patient-years of follow-up 4

Complementary Approach with Vaccination

• Recombinant VZV glycoprotein E vaccine (Shingrix) is recommended for all multiple myeloma patients 1
• Vaccination should be administered as two doses 2-6 months apart 1
• Even with vaccination, antiviral prophylaxis should still be used during high-risk treatments 1
• Live-attenuated VZV vaccines should be avoided in multiple myeloma patients due to their compromised immune system 1

Common Pitfalls and Considerations

• Failure to initiate prophylaxis before starting proteasome inhibitor therapy 6, 7
• Discontinuing prophylaxis too early (should continue at least 6 weeks after stopping proteasome inhibitors) 1
• Poor patient adherence to prophylaxis regimen (the only reported case of VZV reactivation in one study was in a non-compliant patient) 7
• Neglecting to restart prophylaxis when reinitiating treatment with proteasome inhibitors in relapsed disease 1
• Forgetting to provide HSV prophylaxis in patients receiving letermovir for CMV prophylaxis (letermovir lacks anti-HSV activity) 2