Blood cancer and arthritis patients: Rituximab may hinder the effectiveness of COVID-19 vaccines


The research, published today in journal Clinical & Experimental Immunology, was carried out by experts across the Universities of Birmingham and Wolverhampton, The Royal Wolverhampton NHS Trust, University Hospitals

Birmingham NHS Foundation Trust (UHB), Worcestershire Acute Hospitals NHS Trust, and NIHR Clinical Research Network West Midlands (NIHR CRN West Midlands).

It aimed to establish whether a drug called Rituximab – typically used to treat patients with haemato-oncological disease (e.g., certain blood cancers) or rheumatological disease (e.g., certain types of arthritis) – may hinder the effectiveness of COVID-19 vaccines. Treatments such as Rituximab work by killing B cells, which are part of our immune system.

The study involved 80 patients receiving treatment for blood cancers and 36 being treated for diseases such as arthritis. Blood samples were taken before and after vaccination with two doses of either the Pfizer/BioNTech or Oxford/AstraZeneca COVID-19 vaccine between December 2020 and April 2021.

The results were then compared with a control group of healthy age-matched healthcare workers participating in other University of Birmingham-led COVID-19 studies.

The results showed that in the first six months following treatment with Rituximab, only 42.2% of patients with blood cancers and 33.3% of patients with arthritis developed an antibody response to double vaccination – and this was reduced further to 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy.

Also, in those that did have an antibody response to vaccination, the strength of the response was much lower in those with blood cancer or arthritis compared to those in the healthy cohort.

The study showed that six months after treatment, as patients’ bodies began rebuilding B cells, vaccine responsiveness increased to 100% in blood cancer patients, while in arthritis patients there were also ‘progressive increases’ in overall vaccine responsiveness the greater the gap between vaccine and drug treatment.

The research showed similar quality and strength in antibody response with both types of COVID-19 vaccines and across both groups of patients. However, the data also show that shorter intervals (of less than a month) between the first and second vaccine significantly improved both quality and strength of antibody response in blood cancer patients.

Co-corresponding author Professor Supratik Basu, Consultant Haematologist at The Royal Wolverhampton NHS Trust and a researcher at the University of Wolverhampton, explained: “Rituximab targets B cells, which normally produce antibodies. Our hypothesis was that the drug might inadvertently affect the response to COVID-19 vaccination, which may leave patients very vulnerable to serious illness.

These patients are already considered to be high-risk, and therefore it seemed sensible to determine whether the treatment for their pre-existing condition was stopping the body from producing the antibodies it needs to fight the virus. Here we could establish if further vaccination was required or if alternative protection was needed.

As the rate of antibodies in this cohort was extremely low, this should alert clinicians to prioritise these patients for their third booster COVID-19 vaccine, while also giving important reminders about precautions such as hand-washing and social distancing.”

First and co-corresponding author Dr Adrian Shields, a Clinical Immunologist at the University of Birmingham, said: “Rituximab is used all over the world to treat blood cancers and inflammatory diseases. We now know that its use is associated with poor responses to new vaccines. The results from our study emphasise how important it is to undertake further research to improve our understanding of how to use vaccines to achieve the best possible protection for our most clinically vulnerable patients.”

Co-corresponding author Mark Drayson, Professor of Clinical Immunodiagnostics at the University of Birmingham and Honorary Consultant Immunologist at UHB, added: “Our research provides important observations, which suggest that additional immunisations could be necessary at least six months after treatment with drugs that deplete B cells to optimise vaccine responsiveness.

The monitoring of how a patient’s immune response is rebuilding following treatment may also help to ensure optimal vaccine timing. We recommend that individuals who do not respond to COVID-19 vaccines should be evaluated further for secondary immunodeficiency, particularly if treatments that deplete B cells were last administered 18 months or more prior to vaccination.”

Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of B-lymphocytes. CD20 regulates cell cycle initiation; and, possibly, functions as a calcium channel. Rituximab binds to the antigen on the cell surface, activating complement-dependent B-cell cytotoxicity; and to human Fc receptors, mediating cell killing through an antibody-dependent cellular toxicity. B-cells are believed to play a role in the development and progression of rheumatoid arthritis. Signs and symptoms of rheumatoid arthritis are reduced by targeting B-cells and the progression of structural damage is delayed.

FDA Approved Indications

  1. Non-Hodgkin’s lymphoma (NHL) in adult patients with:
  • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy
  • Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent after first line CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy
  • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline- based chemotherapy regimens
  1. Chronic lymphocytic leukemia (CLL), in combination with fludarabine and cyclophosphamide (FC), for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL.
  2. Autoimmune blistering diseases (e.g., pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita and paraneoplastic pemphigus).
  3. Moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate in patients who have inadequate response to one or more TNF antagonist therapies
  4. Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) in combination with glucocorticoids in adults

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