For a patient with multiple myeloma, can subsequent doses of Shingrix (recombinant zoster vaccine) and HBV (hepatitis B virus) vaccine be administered after starting VRd (bortezomib, lenalidomide, and dexamethasone) therapy if the first dose is given at least 2 weeks prior?

Vaccination Timing in Multiple Myeloma Patients Starting VRd Therapy

Direct Answer

No, subsequent doses of Shingrix and hepatitis B vaccine should NOT be administered after VRd therapy has started, as these patients become highly immunocompromised once treatment begins. Both vaccines should ideally be completed at least 2-4 weeks before initiating VRd therapy, or vaccination should be deferred until after treatment completion when immune reconstitution has occurred 1.

Critical Distinction: Shingrix vs. Live Zoster Vaccine

The question specifically asks about Shingrix (recombinant zoster vaccine), which is fundamentally different from the live-attenuated zoster vaccine (Zostavax):

Shingrix (Recombinant Vaccine)

• Shingrix is an inactivated/recombinant vaccine and can be safely administered during immunosuppression, though efficacy may be reduced 1
• The European Myeloma Network recommends Shingrix for all multiple myeloma patients with an 80.4% antibody response rate 1
• Two doses should be given 2-6 months apart 1
• This vaccine can be continued after VRd initiation from a safety standpoint, but immune response will be suboptimal 1

Live Zoster Vaccine (Zostavax)

• Should NOT be given to highly immunocompromised patients including those on active myeloma therapy 1
• Must be administered ≥4 weeks before beginning highly immunosuppressive therapy 1
• Contraindicated once VRd therapy starts 1

Hepatitis B Vaccine Timing

Pre-Treatment Recommendations

• All patients should be screened for hepatitis B (HBs-Ag and anti-HBc antibodies) before starting VRd therapy 1
• Hepatitis B vaccine should ideally be completed before immunosuppression begins 1
• Patients should be vaccinated at least 2 weeks before initiation of chemotherapy 1

Post-Treatment Initiation

• Hepatitis B vaccine (an inactivated vaccine) can be safely administered during VRd therapy, but immune response will be significantly impaired 1
• The standard three-dose series (at 0,1, and 6 months) may need to be repeated or antibody titers checked after completion 1
• Patients on lenalidomide maintenance may show enhanced antibody response due to immune stimulatory effects of IMiDs, though evidence is limited 1

Optimal Vaccination Strategy for VRd Patients

Ideal Pre-Treatment Window

1. Complete all vaccine series ≥4 weeks before VRd initiation for optimal immune response 1
2. Minimum acceptable timing is ≥2 weeks before chemotherapy 1
3. This allows for:
   • Near-optimal immune response (develops in 2-3 weeks) 1
   • Clearance of any vaccine-related reactions 1

If Treatment Cannot Be Delayed

• Inactivated vaccines (Shingrix, hepatitis B) can be given but with reduced efficacy 1
• Annual vaccination with inactivated influenza vaccine is still recommended even during intensive chemotherapy 1
• Patients receiving intensive chemotherapy or anti-B-cell antibodies within 6 months are unlikely to respond but unlikely to be harmed 1

Alternative Timing Options

1. Upon achievement of best response (3-6 months after completion of chemotherapy) 1
2. 3-6 months after autologous transplantation 1
3. During lenalidomide maintenance when immune function may be partially restored 1

Critical Safety Considerations

VRd-Specific Risks

• Bortezomib significantly increases risk of VZV reactivation, making zoster vaccination particularly important 1
• Daratumumab (if added to VRd) increases risk of HBV reactivation in patients with resolved infection 2
• VRd induces profound immunosuppression, classifying patients as "highly immunocompromised" 1

Common Pitfall to Avoid

• Do not confuse Shingrix (recombinant, can be given during treatment) with live zoster vaccine (contraindicated during treatment) 1
• The live zoster vaccine has only 63% estimated efficacy and should not be used if Shingrix is available 1

Practical Algorithm

For patients about to start VRd:

1. ≥4 weeks before VRd: Complete all vaccine series (Shingrix 2 doses 2-6 months apart, hepatitis B 3 doses at 0,1,6 months) 1

2. 2-4 weeks before VRd: Acceptable window for first doses if treatment cannot be delayed 1

3. After VRd starts:

   • Shingrix subsequent doses: Can proceed but expect reduced response 1
   • Hepatitis B subsequent doses: Can proceed but expect reduced response 1
   • Check antibody titers after completion 1

4. During maintenance or after treatment: Consider revaccination or booster doses with antibody titer confirmation 1