Susceptibility Factors for VZV Reactivation in Multiple Myeloma Patients
Multiple myeloma patients are highly susceptible to Varicella Zoster Virus (VZV) reactivation primarily due to their immunosuppressive treatments, with a hazard ratio of 14.8 for VZV reactivation compared to the general population. 1
Primary Risk Factors
- Proteasome inhibitor therapy (bortezomib, carfilzomib) significantly increases the risk of VZV reactivation during active treatment 1
- Anti-CD38 monoclonal antibody therapy (daratumumab) is associated with higher VZV reactivation risk 1
- High-dose melphalan followed by autologous stem cell transplantation (ASCT) substantially increases VZV reactivation risk 1
- High doses of glucocorticosteroids contribute to increased VZV reactivation risk 1
- Impaired cellular immunity is the principal risk factor for VZV disease in these patients 1
Pathophysiology
- VZV reactivation occurs when the latent virus residing in sensory ganglions becomes active due to immunosuppression 1
- The active virus production leads to spread alongside the axons to the skin area innervated by the affected ganglion 1
- This results in inflammation, blisters, and pain characteristic of herpes zoster 1
Disease-Related Factors
- Multiple myeloma itself causes significant immune impairment and dysfunction of the adaptive immune response 1
- The malfunction of immune regulation of plasma cells contributes to increased infection risk 1
- The combination of disease-related and treatment-related immunosuppression creates a high-risk environment for VZV reactivation 1
Treatment-Specific Risks
- Bortezomib therapy: Studies have shown VZV reactivation rates of 10-60% in patients without prophylaxis 2, 3
- Autologous stem cell transplantation: VZV reactivation risk extends through the first year post-transplant 1
- T-cell depleting agents: Patients receiving these therapies have intermediate to high risk for viral reactivation 1
- Bispecific antibody therapy: Emerging data suggests increased risk of opportunistic infections including VZV reactivation 1
Prevention Strategies
- Prophylaxis with acyclovir (400 mg once to three times daily) or valacyclovir (500 mg daily) effectively prevents VZV reactivation in patients receiving bortezomib-based therapies 4, 2, 5
- Prophylaxis should be considered for at least 6-12 months post-autologous stem cell transplantation 1
- Recombinant VZV glycoprotein E vaccine is preferred over live-attenuated VZV vaccine for multiple myeloma patients 1
Clinical Implications
- Without prophylaxis, multiple myeloma patients have significantly higher rates of VZV reactivation than the general population 1
- VZV reactivation can lead to treatment interruptions and decreased quality of life 4, 5
- Prophylactic strategies have been shown to effectively reduce the risk of VZV reactivation in this high-risk population 4, 2, 5