Which inactivated vaccines should be given and which live vaccines should be deferred for a patient who received pneumococcal and influenza vaccines before rituximab induction and is now scheduled for a third maintenance rituximab infusion?

Vaccination Strategy for Patient on Maintenance Rituximab

For a patient already on maintenance rituximab who previously received pneumococcal and influenza vaccines, administer influenza vaccine on schedule without delay, but defer all other inactivated vaccines (including pneumococcal boosters) until just before the next rituximab dose is due, then delay that rituximab infusion by 2 weeks after vaccination. 1

Influenza Vaccination: Proceed Immediately

• Administer the annual inactivated influenza vaccine on schedule without deferring to rituximab timing. 1
• This is the only vaccine that should not be delayed in rituximab-treated patients, as the seasonal nature and public health importance outweigh the reduced immunogenicity concerns. 1
• Use only inactivated (intramuscular) influenza vaccine—never live attenuated intranasal formulations. 2, 3

All Other Inactivated Vaccines: Strategic Timing Required

• Defer any additional inactivated vaccines (including pneumococcal boosters, Tdap, hepatitis B, or others) until just before the next scheduled rituximab maintenance dose. 1
• Administer these vaccines when the next rituximab infusion is due, then delay that rituximab dose by at least 2 weeks after vaccination to maximize immune response. 1, 4, 5
• This timing strategy capitalizes on the period of maximal B-cell recovery (just before the next rituximab dose) to optimize vaccine immunogenicity. 1

Live Vaccines: Absolute Contraindication

• Never administer live attenuated vaccines (MMR, varicella, zoster, intranasal influenza) during rituximab treatment or within 6 months after the last dose. 4, 3
• The FDA label explicitly contraindicates live virus vaccinations during rituximab treatment due to severe immunosuppression. 3

Understanding the Immunologic Rationale

• Rituximab causes profound B-cell depletion that severely impairs vaccine responses for up to 6 months after each infusion. 4, 6, 7
• Research demonstrates that only 21-29% of rituximab-treated patients achieve adequate antibody responses to pneumococcal and Haemophilus vaccines at 6 months post-treatment, compared to 67-83% of controls. 6
• T-cell dependent responses (like tetanus) are relatively preserved (39% response rate), but T-cell independent responses (pneumococcal polysaccharide) and neoantigen responses are markedly impaired (47-57% response rates). 8
• The window just before the next rituximab dose represents the period of maximal B-cell recovery and therefore optimal vaccine responsiveness. 1, 9

Critical Pitfalls to Avoid

• Do not assume prior vaccination provides adequate ongoing protection—rituximab may deplete existing antibody-producing plasma cells over time, though this patient's pre-rituximab vaccination was appropriately timed. 4
• Do not vaccinate in the immediate post-rituximab period (first 4-6 months after infusion)—this represents the nadir of immune function when vaccine responses are poorest. 6, 7, 9
• Do not hold influenza vaccine waiting for optimal rituximab timing—this is the one exception where on-schedule vaccination is recommended despite suboptimal immunogenicity. 1

Monitoring Considerations

• Consider measuring antibody titers 4 weeks after any vaccination to confirm adequate immune response, particularly for pneumococcal serotype-specific antibodies. 4
• If titers are inadequate, revaccination may be considered after rituximab is discontinued or during a prolonged treatment holiday, though evidence for this approach is limited. 4