Immune Response After SARS-CoV-2 Vaccination in a Context of Non-Hodgkin Lymphoma (LYMPHO-CoVac)

The specific immune response to SARS-CoV-2 includes a humoral response - specific IgM appearing 5 days after the onset of symptoms while IgG appears after 14 days - and a T lymphocyte component, with specific activated CD8 and CD4 T lymphocytes (Dan JM et al., Science 2021).

Mortality from infection varies greatly depending on the age of the affected subjects and their comorbidities including a history of cancer (Liang W et al, 2020). Among these cancers, a history of malignant hemopathy in the 5 years preceding the onset of Covid-19 increases the risk of death by a factor of 3 (OpenSAFELY collaborative 2020). Among them, lymphoid hemopathies induce hypogammaglobulinemia and / or lymphopenia. These factors combined with chemotherapy and immunotherapy treatments promote the development of infections in affected individuals. Among these, are the anti-CD20 monoclonal antibodies, widely prescribed for treating B-cell non-Hodgkin lymphomas (B-NHL). They induce a deep and lasting B-cell lymphopenia, which can promote infections (Maschmeyer G et al, 2019). They reduce the production of antibodies and the constitution of memory responses to a new pathogen or to a vaccination. In addition, B lymphocytes likely have a key immunomodulatory role in the control of viral infections.

We conducted a retrospective study in 89 patients with lymphoma and Covid-19 after the first phase of the epidemic in different centers in the Île-de-France and eastern France regions (Lamure S et al. , 2020). With a 6-month follow-up, we showed a pejorative prognostic impact of anti-CD20 monoclonal antibody treatment on Covid-19-related mortality (Duléry et al, 2021).

Vaccination of these at-risk patients is therefore essential. A growing concern is how patients with B-NHL who have been vaccinated with a SARS-CoV-2 mRNA vaccine are protected against infection, depending on whether or not they have received anti-CD20 monoclonal drugs and / or chemotherapy.

Knowing the medium-term immunological evolution after vaccination against SARS-CoV-2 in patients with B-cell NHL is necessary in order to be able to adapt the therapeutic and vaccine recommendations.

The main objective of this study is to determine how recent treatment (in the year before vaccination) with anti-CD20 monoclonal antibody modifies the immune response after vaccination against SARS-CoV-2 in adults with B-NHL compared to patients who have not recently been exposed to this immunotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Vaccination Failure; Non-hodgkin Lymphoma,B Cell
• Intervention / Treatment: Other: Immunological analyses

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult aged at least 18 years old

  • Having received (at least) two injections of anti-SARS-CoV-2 messenger RNA vaccine (Pfizer and / or Moderna)
  • Affiliated to social security
  • consenting to the study
  • Concenring cases only: Be or have been affected by B-NHL in remission, active surveillance or during first-line or second-line treatment, regardless of this treatment

Exclusion Criteria:

Patient less than 18 years old

• Patient with protective measure (curatorship, guardianship, safeguard of justice, deprived of liberty, in an emergency situation)
• Patient unable to express their consent
• Pregnant or breastfeeding woman
• Patient refusing to participate
• Concenring cases: Patient whose life expectancy related to B-NHL is less than 6 months, History of allogeneic hematopoietic stem cell transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cases; Patients with a history of B-NHL	Other: Immunological analyses; Immunological analyses will be performed at inclusion in both arms
Other: Controls; Spouses of cases	Other: Immunological analyses; Immunological analyses will be performed at inclusion in both arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of humoral (especially anti-SARS-CoV-2 antibody levels) and T cell memory responses in adult patients with B-NHL depending on whether or not they were exposed to anti-CD20 monoclonal antibody treatment in the year before vaccination.	at inclusion

Collaborators and Investigators

• Sponsor: Versailles Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 20, 2021
• Primary Completion (Anticipated): March 20, 2022
• Study Completion (Anticipated): August 20, 2022

Study Registration Dates

• First Submitted: September 13, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 20, 2021

Study Record Updates

• Last Update Posted (Actual): September 20, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: P21/08 - LYMPHO-CoVac

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No