Impaired Humoral Immunity to SARS-CoV-2 Vaccination in Non-Hodgkin Lymphoma and CLL Patients

  1. Catherine Diefenbach
  2. Jessica Caro
  3. Akiko Koide
  4. Michael Grossbard
  5. Judith D. Goldberg
  6. Bruce Raphael
  7. Kenneth Hymes
  8. Tibor Moskovits
  9. Maxim Kreditor
  10. David Kaminetzky
  11. Shella Saint Fleur-Lominy
  12. Jun Choi
  13. Sara A. Thannickal
  14. Kenneth A. Stapleford
  15. Shohei Koide

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Abstract

Patients with hematologic malignancies are a high priority for SARS-CoV-2 vaccination, yet the benefit they will derive is uncertain. We investigated the humoral response to vaccination in 53 non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or CLL patients. Peripheral blood was obtained 2 weeks after first vaccination and 6 weeks after second vaccination for antibody profiling using the multiplex bead-binding assay. Serum IgG, IgA, and IgM antibody levels to the spike specific receptor binding domain (RBD) were evaluated as a measure of response. Subsequently, antibody-positive serum were assayed for neutralization capacity against authentic SARS-CoV-2. Histology was 68% lymphoma and 32% CLL; groups were: patients receiving anti-CD20-based therapy (45%), monitored with disease (28%), receiving BTK inhibitors (19%), or chemotherapy (all HL) (8%). SARS-CoV-2 specific RBD IgG antibody response was decreased across all NHL and CLL groups: 25%, 73%, and 40%, respectively. Antibody IgG titers were significantly reduced (p < 0.001) for CD20 treated and targeted therapy patients, and (p = 0.003) for monitored patients. In 94% of patients evaluated after first and second vaccination, antibody titers did not significantly boost after second vaccination. Only 13% of CD20 treated and 13% of monitored patients generated neutralizing antibodies to SARS-CoV-2 with ICD50s 135 to 1767, and 445 and > 10240. This data has profound implications given the current guidance relaxing masking restrictions and for timing of vaccinations. Unless immunity is confirmed with laboratory testing, these patients should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.

Statement of Translational Relevance

Non Hodgkin lymphoma (NHL) and Chronic Lymphocytic leukemia (CLL) patients who are treated with anti-CD20 antibody therapy, BTK inhibitor therapy, or who are monitored with active disease, have decreased antibody response to SARS-CoV-2 vaccination and decreased antibody titers compared to healthy controls. Antibody titers do not boost following second vaccination, and very few patients generate neutralizing antibodies against SARS-CoV-2. This data is of particular importance, given the recent guidance from the CDC that vaccinated patients no longer need to be masked indoors as well as outdoors. Patients with NHL or CLL who fall into these categories should not consider their immunity from vaccination to be assured. If infected with SARS-CoV-2, they should be a high priority for monoclonal antibody directed therapy. Unless immune response to vaccination is confirmed with laboratory testing, they should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.

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  1. ScreenIT

    SciScore for 10.1101/2021.06.02.21257804: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The Institutional Review Board of the Perlmutter Cancer Center at NYU Langone Health reviewed and approved the study, which was conducted according to the Declaration of Helsinki and International Harmonization Guidelines for Good Practice.
    Consent: All patients signed informed consent for the study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    For virus neutralization assays, icSARS-CoV-2-mNG (isolate USA/WA/1/2020 expressing a mNeon Green reporter), was obtained from the UTMB World Reference Center for Emerging Viruses and Arboviruses(15) and amplified once in Vero E6 cells (ATCC CRL-1586) to generated a working stock.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    We detected bound IgG, IgA and IgM using anti-human IgG-Alexa 488 (Jackson Immunoresearch catalog number 109-545-098), anti-human IgA-PE (Jackson Immunoresearch; catalog number 109-115-011) and anti-human IgM-DyLight405 (Jackson Immunoresearch; catalog number 709-475-073), diluted in PBS with 0.1 % Tween 20 and 1 % BSA to 1:800, 1:100 and 1:200 respectively, on a Yeti ZE5 Cell Analyzer (Bio-Rad) and analyzed the data using FlowJo (BD, version 10.7.1).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.06.02.21257804v1 on medRxiv