What is the recommended gap between administering the influenza vaccine and rituximab (rituximab) infusion in an adult patient with non-Hodgkin's lymphoma or an autoimmune disease?

Timing of Influenza Vaccine and Rituximab Infusion

Administer the influenza vaccine on schedule regardless of rituximab timing, then delay the next rituximab dose for at least 2 weeks after vaccination if disease activity permits. 1

Optimal Vaccination Strategy

The 2022 American College of Rheumatology guidelines provide clear direction for this clinical scenario:

• Give influenza vaccination on schedule without waiting for rituximab timing to align, as the seasonal nature of influenza makes timely vaccination critical 1
• Hold rituximab for at least 2 weeks after vaccination to allow time for immune response development, assuming disease activity allows 1
• Ideally time vaccination when the next rituximab dose is due, then delay that dose by at least 2 weeks post-vaccination 1

Rationale for This Approach

Why Not Delay Vaccination

• Influenza vaccine responses are greater when administered later (rather than earlier) after rituximab, but the seasonal window for influenza vaccination takes priority over optimal immunologic timing 1
• Missing the influenza season poses greater morbidity and mortality risk than receiving a potentially suboptimal vaccine response 1

Evidence of Rituximab's Impact on Vaccine Response

• Rituximab profoundly impairs humoral vaccine responses for 6-9 months after treatment, with B-cell recovery typically occurring 9-12 months post-therapy 1, 2
• Studies demonstrate that none of 67 lymphoma patients on rituximab achieved protective antibody titers to influenza vaccine, compared to 82% of controls 3
• However, patients may still mount T-cell responses to vaccination even when antibody responses are blunted, though the protective value of this is uncertain 1

Special Considerations for Non-Hodgkin Lymphoma vs Autoimmune Disease

The evidence base primarily derives from rheumatologic populations, but the principles apply to lymphoma patients:

• For autoimmune disease patients: The ACR guidelines 1 directly address this population with conditional recommendations
• For lymphoma patients: The same immunologic principles apply, as rituximab causes identical B-cell depletion regardless of underlying diagnosis 2, 3
• Both populations experience prolonged B-cell depletion lasting 6-9 months with full recovery at 9-12 months 1, 2

Alternative Approach for Non-Influenza Vaccines

For other non-live vaccines (pneumococcal, COVID-19, etc.), a different strategy applies:

• Defer vaccination until the next rituximab dose is due, then hold rituximab for at least 2 weeks after vaccination 1
• This maximizes vaccine immunogenicity since these vaccines are not seasonally constrained 1

Critical Pitfalls to Avoid

• Do not withhold influenza vaccination waiting for "optimal" rituximab timing—this risks missing the influenza season entirely 1
• Do not assume adequate protection from vaccination in rituximab-treated patients; counsel patients about continued infection prevention measures 3
• Do not delay rituximab indefinitely—the 2-week hold is sufficient if disease activity allows; longer delays risk disease flare 1
• Consider revaccination later when B-cell recovery occurs (9-12 months post-rituximab) for improved immunogenicity 1

When Rituximab Cannot Be Delayed

If disease activity does not permit holding rituximab:

• Proceed with vaccination anyway to provide at least partial protection through potential T-cell responses 1
• Continue rituximab on schedule without the 2-week delay 1
• Counsel patients about potentially reduced vaccine efficacy and need for continued preventive measures 3