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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1510942
This article is part of the Research Topic SARS-CoV-2 Vaccines Beyond the Pandemic Era View all 9 articles

SARS-CoV-2 immune responses in patients with multiple myeloma and lenalidomide maintenance therapy

Provisionally accepted
Ioana Martac Ioana Martac 1Sina Beer Sina Beer 1Aileen Schenk Aileen Schenk 1Osama Ahmad Osama Ahmad 1Claus Philipp Maier Claus Philipp Maier 1,2Gülay Demirel Gülay Demirel 1Beate Preuß Beate Preuß 1Reinhild Klein Reinhild Klein 1Anna M. Stanger Anna M. Stanger 1Britta Besemer Britta Besemer 1Luca Hensen Luca Hensen 1*Claudia Lengerke Claudia Lengerke 1
  • 1 Department for internal Medicine II, Universitiy Hospital Tübinge, Tübingen, Germany
  • 2 Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany

The final, formatted version of the article will be published soon.

    Multiple myeloma (MM) is an uncontrolled plasma cell proliferation in the bone marrow, leading to immune dysregulation with impaired humoral immune responses. Conversely, cellular-based responses play a vital role in MM patients. However, the extent and duration of cellular-induced protection remain unclear to date. Here, immunomodulatory drugs (IMiDs) like Lenalidomide (Lena) become interesting, as they may have stimulatory effects on T-cell functioning. In this study we investigated immune responses elicited by COVID-19 vaccine or infection comparing 43 healthy volunteers (avg. 35y, 72.1% female, 81.4% previously COVID-19 infected), with 41 MM patients under Lena maintenance therapy (avg. 63.8y, 51.2% female, 61% previously COVID-19 infected). Humoral responses to SARS-CoV-2 spike (S), spike-RBD, and nucleocapsid (N) were measured via ELISA in subjects’ plasma. Freshly isolated PBMCs, incubated with SARS-CoV-2 peptides (N, S), activation induced marker (AIM) assays and flow cytometry, allowed us to assess cellular responses (CD8+ T, T(F)H: CD4+ T (follicular) helper). Whereas healthy controls showed significant better humoral responses (N IgA p<0.001), T cell responses were robust in the MM group (higher S-act. TH, p<0.001). Stratified by COVID-19 status, the MM group showed higher N-act. TH (p=0.03). These results were unchanged comparing a Lena intake with Lena break around vaccination. Taken together, MM patients under Lena therapy exhibit weakened antibody production but present a robust T cell response following SARS-COV-2 infection or vaccination. Our results highlight the importance of vaccination in this subgroup and moreover, argue against a Lena intake break around the time of vaccination.

    Keywords: Multiple Myeloma, Immunomodulatory therapy, Lenalidomide, Cellular immune responses, vaccine response

    Received: 14 Oct 2024; Accepted: 29 Nov 2024.

    Copyright: © 2024 Martac, Beer, Schenk, Ahmad, Maier, Demirel, Preuß, Klein, Stanger, Besemer, Hensen and Lengerke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Luca Hensen, Department for internal Medicine II, Universitiy Hospital Tübinge, Tübingen, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.