Efficacy of COVID-19 Vaccination in Patientstreated With Anti-CD20 for Follicular Lymphoma or Mantle Cell Lymphoma

Post-vaccination Immunization Against SARS-CoV-2 in Patients Undergoing Maintenance With Anti-CD20 Antibodies for Follicular Lymphoma (FL) or Mantle Cell

The anti-CD20 monoclonal antibodies, rituximab (R) and obinutuzumab (G), are used as standard maintenance therapy every 2 months for 2 to 3 years in patients with follicular lymphoma (FL) or mantle cell lymphoma (MCL).

This treatment is associated with profound and prolonged B lymphopenia, hypogammaglobulinemia and increased infections. Severe forms of COVID-19 on Rituximab with prolonged carriage of the virus have been reported due to significant impairment of humoral immunity in this context of maintenance therapy.

Therefore, during the COVID-19 epidemic, clinicians are faced with the question of whether to discontinue maintenance therapy or continue treatment. However, the half-life of rituximab is 29 days and lymphopenia continues for up to 9-12 months after stopping injections. Therefore, it is not clear that discontinuation of maintenance therapy will alter the risk of severe SARS-CoV-2.

However, post-vaccination immunization against SARS-CoV-2 by an mRNA vaccine is not known in this context of prolonged treatment with rituximab or obinutuzumab. It is however well established that post-vaccination responses against diphtheria, tetanus, pneumococcus, HBV, or influenza in particular are altered after anti-CD20 antibodies. If the humoral response is crucial in the post-vaccination response, it is also suggested that the preservation of innate immunity and the CD8 response, unaltered by anti-CD20, could also play an important role in the post-vaccination response and virus clearance.

The aim of our study is to evaluate the humoral and post-vaccination T-cell response based on serological data and T-cell production of interferon gamma in response to SARS-CoV-2 specific antigens (Elispot interferon gamma) in this group of patients treated for lymphoma with a long-term anti-CD20 antibody.

Inclusion Criteria:

• Age superior to 18 years old
• Patient undergoing maintenance treatment for Mantle Cell Lymphoma or Follicular Lymphoma treated with rituximab or obinutuzumab in complete remission or stable disease between injection #1 and injection #13 or 19 (end of second year or third year)
• Inform consent signed

Exclusion Criteria:

• Documented history of SARS-Cov-2 infection less than 3 months old
• Progressive lymphoma
• Contraindication SARS-Cov-2 vaccination (allergy)
• Refusal of SARS-CoV-2 vaccination
• Patient who has been off rituximab or obinutuzumab therapy for more than 6 months
• Patient not covered by health system
• Pregnant or nursing woman