Rituximab is becoming a frequently used treatment option for many patients with complex medical needs, including in oncology and rheumatology. It is an immune suppressive medication which greatly impacts the production and functionality of immune cells, including the near complete depletion of B-cells. Once treatment with rituximab has been completed, recovery of immune cell function can take 3-12 months, and even longer in some cases. It may be used as a once-only dose or as a long term therapy.

Due to the effects on lymphocytes, patients on rituximab therapy are considered immune suppressed and are at a greater risk of vaccine preventable diseases. However, recommendations for immunisation of these patients is complicated by the inability to produce an immune response to vaccines without functioning B- and T-cells.

Many patients on rituximab are also receiving concomitant immunoglobulin therapy. As this is a blood product, it further complicates the immunisation recommendations involving live-attenuated vaccines.

Prior to commencing treatment

Where possible please ensure patients are up to date for their age with the current immunisation schedule. Ideally inactivated vaccines should be completed at least 1 week prior, and any live-attenuated vaccines should be completed a minimum of 4 weeks prior to commencing treatment. The same principle also applies to COVID-19 vaccines.

During treatment

Due to lack of immune cell function, all future immunisations should be withheld whilst on rituximab. An immunisation medical exemption form should be completed where appropriate to ensure that the patient is not considered overdue [see resources].

The exception to this, may be for influenza and COVID-19 vaccines. Some studies have indicated that a partial immune response to the influenza vaccine in patients receiving rituximab therapy may occur. For this reason MVEC recommends that patients continue to be immunised against influenza whilst on therapy and receive 2 doses of the age-appropriate vaccine annually, minimum of 4 weeks apart (regardless of age or vaccine history).

Due to the potential risk for severe COVID-19 disease and its complications in this population, which may outweigh the lack of vaccine response, COVID-19 vaccination whilst on rituximab could be considered.

COVID-19 vaccination and rituximab

Studies are still ongoing to determine optimum timing and vaccine efficacy in patients on rituximab. However, based on evidence from other vaccines, the assumption is that there is a diminished response to COVID-19 vaccination.

Therefore, important principles to consider when considering COVID-19 vaccination in this group of patients include:

  • It is not recommended to delay initiation or disrupt optimum timing of rituximab if being used for cancer treatment
  • Due to its immunosuppressive effects, patients on rituximab are at higher risk of severe COVID-19 disease and poor COVID-19 disease outcomes

As such, COVID-19 vaccination could be performed as close to the end of a rituximab cycle as possible, or prior to the initiation of therapy. There is no current data to inform optimum timing of two-dose COVID-19 vaccination regimes and intervals.

Refer to MVEC: COVID-19 vaccines in people with immunocompromise

Immunisation of household contacts

All close contacts should ensure that they are up to date with the routine immunisation schedule, including MMR, varicella and pertussis vaccines. Annual Influenza vaccination is strongly recommended. COVID-19 vaccination is encouraged.

Serology

There is no need to check serology pre- or post-rituximab therapy. There is currently no established immune correlate of protection for COVID-19.

Patients should be aware of their immune suppression and avoid potential exposures to vaccine preventable diseases. The need to continue preventative measures such as social distancingmask wearing and hand hygiene should be discussed. Medical advice should be sought if exposure does occur [see resources for post-exposure immunoglobulin recommendations].

Post treatment

Post the completion of rituximab therapy, immunoglobulin and B-cell levels should be checked every 3 months. Once both levels have returned to normal AND ≥ 6 months post treatment has lapsed (whichever is later), immunisation with both inactivated and live-attenuated vaccines can recommence. For patients who have received immunoglobulin alongside their rituximab, specific intervals are recommended between the administration of live-attenuated vaccines and blood products/immunoglobulin [refer to MVEC: Live-attenuated vaccines and immunoglobulins or blood products]. Any previous vaccine history (routine vaccines) should be disregarded due to the loss of immune memory. There is currently no recommendation for additional booster doses of COVID-19 vaccines.

Please refer to MVEC: Post rituximab therapy immunisation guideline for re-immunisation recommendations.

Resources

Authors: Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children’s Research Institute), Daryl Cheng (Senior Research Fellow, Murdoch Children’s Research Institute) and Theresa Cole (Consultant, Allergy and Immunology, The Royal Children’s Hospital)

Reviewed by: Rachael McGuire (MVEC Education Nurse Coordinator) and Daryl Cheng (MVEC Medical Lead)

Date: June 2021

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy. You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.