Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 153 No. 6 (2023)

Humoral and cellular BNT162b2 mRNA-based booster vaccine-induced immunity in patients with multiple myeloma and persistence of neutralising antibodies: results of a prospective single-centre cohort study

  • Tobias Silzle
  • Christian R. Kahlert
  • Werner C. Albrich
  • Susanne Nigg
  • Ruth Demmer Steingruber
  • Christoph Driessen
  • Stefanie Fischer
DOI
https://doi.org/10.57187/smw.2023.40090
Cite this as:
Swiss Med Wkly. 2023;153:40090
Published
15.06.2023

Summary

BACKGROUND: Currently available messenger ribonucleic acid (mRNA)-based vaccines against coronavirus disease (COVID-19) have been shown to be effective even in highly immunocompromised hosts, including patients with multiple myeloma. However, vaccination failure can be observed in all patient groups.

METHODS: This prospective study longitudinally assessed the humoral and cellular responses to a third booster dose of BNT162b2 mRNA-based vaccine in patients with myeloma (n = 59) and healthy controls (n = 22) by measuring the levels of anti-spike (S) antibodies (electro-chemiluminescence immunoassay) including neutralising antibodies and specific T-cells (enzyme-linked immunospot assay) following booster administration.

RESULTS: The third booster dose showed a high immunogenicity on the serological level among the patients with multiple myeloma (median anti-S level = 41 binding antibody units [BAUs]/ml pre-booster vs 3902 BAU/ml post-booster, p <0.001; increase in the median neutralising antibody level from 19.8% to 97%, p <0.0001). Four of five (80%) patients with a complete lack of any serological response (anti-S immunoglobulin level <0.8 BAU/ml) after two vaccine doses developed detectable anti-S antibodies after booster vaccination (median anti-S level = 88 BAU/ml post-booster).

T-cell responses were largely preserved among the patients with multiple myeloma with no difference from the healthy controls following baseline vaccination (median spot-forming units [SFU]/106 of peripheral blood mononuclear cells = 193 vs 175, p = 0.711); these responses were augmented significantly after booster administration among the patients with multiple myeloma (median SFU/106 of peripheral blood mononuclear cells = 235 vs 443, p <0.001). However, the vaccination responses remained highly heterogeneous and diminished over time, with insufficient serological responses occurring even after booster vaccination in a few patients irrespective of the treatment intensity.

CONCLUSIONS: Our data demonstrate improvements in humoral and cellular immunity following booster vaccination and support the assessment of the humoral vaccine response in patients with multiple myeloma until a threshold for protection against severe COVID-19 is validated. This strategy can allow the identification of patients who might benefit from additional protective measures (e.g. pre-exposure prophylaxis via passive immunisation).

References

  1. Tomalka JA, Suthar MS, Deeks SG, Sekaly RP. Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses. Nat Immunol. 2022 Mar;23(3):360–70. 10.1038/s41590–022–01130–4 10.1038/s41590-022-01130-4 DOI: https://doi.org/10.1038/s41590-022-01130-4
  2. Ludwig H, Sonneveld P, Facon T, San-Miguel J, Avet-Loiseau H, Mohty M, et al. COVID-19 vaccination in patients with multiple myeloma: a consensus of the European Myeloma Network. Lancet Haematol. 2021 Dec;8(12):e934–46. 10.1016/S2352–3026(21)00278–7 10.1016/S2352-3026(21)00278-7 DOI: https://doi.org/10.1016/S2352-3026(21)00278-7
  3. Moss P. The T cell immune response against SARS-CoV-2. Nat Immunol. 2022 Feb;23(2):186–93. 10.1038/s41590–021–01122–w 10.1038/s41590-021-01122-w DOI: https://doi.org/10.1038/s41590-021-01122-w
  4. Sahin U, Muik A, Vogler I, Derhovanessian E, Kranz LM, Vormehr M, et al. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature. 2021 Jul;595(7868):572–7. 10.1038/s41586–021–03653–6 10.1038/s41586-021-03653-6 DOI: https://doi.org/10.1038/s41586-021-03653-6
  5. Bange EM, Han NA, Wileyto P, Kim JY, Gouma S, Robinson J, et al. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat Med. 2021 Jul;27(7):1280–9. 10.1038/s41591–021–01386–7 10.1038/s41591-021-01386-7 DOI: https://doi.org/10.1038/s41591-021-01386-7
  6. Riester E, Findeisen P, Hegel JK, Kabesch M, Ambrosch A, Rank CM, et al. Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay. J Virol Methods. 2021 Nov;297:114271. 10.1016/j.jviromet.2021.114271 DOI: https://doi.org/10.1016/j.jviromet.2021.114271
  7. Barrière J, Carles M, Audigier-Valette C, Re D, Adjtoutah Z, Seitz-Polski B, et al. Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: should humoral responses be monitored? A position article. Eur J Cancer. 2022 Feb;162:182–93. 10.1016/j.ejca.2021.12.011 DOI: https://doi.org/10.1016/j.ejca.2021.12.011
  8. Murray MJ, McIntosh M, Atkinson C, Mahungu T, Wright E, Chatterton W, et al. Validation of a commercially available indirect assay for SARS-CoV-2 neutralising antibodies using a pseudotyped virus assay. J Infect. 2021 May;82(5):170–7. 10.1016/j.jinf.2021.03.010 DOI: https://doi.org/10.1016/j.jinf.2021.03.010
  9. Hodcroft, E. Overview of Variants in Countries.
  10. Gagelmann N, Passamonti F, Wolschke C, Massoud R, Niederwieser C, Adjallé R, et al. Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis. Haematologica. 2022 Aug;107(8):1840–9. 10.3324/haematol.2021.280163 DOI: https://doi.org/10.3324/haematol.2021.280163
  11. Ito Y, Honda A, Kurokawa M. COVID-19 mRNA Vaccine in Patients With Lymphoid Malignancy or Anti-CD20 Antibody Therapy: A Systematic Review and Meta-Analysis. Clin Lymphoma Myeloma Leuk. 2022 Aug;22(8):e691–707. 10.1016/j.clml.2022.03.012 DOI: https://doi.org/10.1016/j.clml.2022.03.012
  12. Wang, X.; Sima, L. Antibody Response after Vaccination against SARS–CoV–2 in Adults with Hematological Malignancies: A Systematic Review and Meta–Analysis. J Infect 2022, S0163–4453(22)00674–0, doi:10.1016/j.jinf.2022.11.013. DOI: https://doi.org/10.1016/j.jinf.2022.11.013
  13. Frankel AE, Capozzola T, Andrabi R, Ahn C, Zhou P, He WT, et al. The Effects of an mRNA Covid-19 Vaccine Booster on Immune Responses in Cancer-Bearing Veterans. Med Res Arch. 2022 Jul;10(7): 10.18103/mra.v10i7.2932 DOI: https://doi.org/10.18103/mra.v10i7.2932
  14. Ntanasis-Stathopoulos I, Karalis V, Gavriatopoulou M, Malandrakis P, Sklirou AD, Eleutherakis-Papaiakovou E, et al. Second Booster BNT162b2 Restores SARS-CoV-2 Humoral Response in Patients With Multiple Myeloma, Excluding Those Under Anti-BCMA Therapy. HemaSphere. 2022 Jul;6(8):e764. 10.1097/HS9.0000000000000764 DOI: https://doi.org/10.1097/HS9.0000000000000764
  15. Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, Briasoulis A, Gumeni S, Malandrakis P, et al. Booster BNT162b2 optimizes SARS-CoV-2 humoral response in patients with myeloma: the negative effect of anti-BCMA therapy. Blood. 2022 Mar;139(9):1409–12. 10.1182/blood.2021014989 DOI: https://doi.org/10.1182/blood.2021014989
  16. Enssle JC, Campe J, Büchel S, Moter A, See F, Grießbaum K, et al. Enhanced but variant-dependent serological and cellular immune responses to third-dose BNT162b2 vaccination in patients with multiple myeloma. Cancer Cell. 2022 Jun;40(6):587–9. 10.1016/j.ccell.2022.05.003 DOI: https://doi.org/10.1016/j.ccell.2022.05.003
  17. Re D, Seitz-Polski B, Brglez V, Carles M, Graça D, Benzaken S, et al. Humoral and cellular responses after a third dose of SARS-CoV-2 BNT162b2 vaccine in patients with lymphoid malignancies. Nat Commun. 2022 Feb;13(1):864. 10.1038/s41467–022–28578–0 10.1038/s41467-022-28578-0 DOI: https://doi.org/10.1038/s41467-022-28578-0
  18. Storti P, Marchica V, Vescovini R, Franceschi V, Russo L, Notarfranchi L, et al. Immune response to SARS-CoV-2 mRNA vaccination and booster dose in patients with multiple myeloma and monoclonal gammopathies: impact of Omicron variant on the humoral response. OncoImmunology. 2022 Sep;11(1):2120275. 10.1080/2162402X.2022.2120275 DOI: https://doi.org/10.1080/2162402X.2022.2120275
  19. Wagner A, Garner-Spitzer E, Schötta AM, Orola M, Wessely A, Zwazl I, et al. SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients - A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease. Front Immunol. 2022 May;13:889138. 10.3389/fimmu.2022.889138 DOI: https://doi.org/10.3389/fimmu.2022.889138
  20. Aleman A, Van Oekelen O, Upadhyaya B, Beach K, Kogan Zajdman A, Alshammary H, et al.; PVI/MM/Seronet Study Group. Augmentation of humoral and cellular immune responses after third-dose SARS-CoV-2 vaccination and viral neutralization in myeloma patients. Cancer Cell. 2022 May;40(5):441–3. 10.1016/j.ccell.2022.03.013 DOI: https://doi.org/10.1016/j.ccell.2022.03.013
  21. Chung A, Banbury B, Vignali M, Huang CY, Asoori S, Johnson R, et al. Antibody and T-cell responses by ultra-deep T-cell receptor immunosequencing after COVID-19 vaccination in patients with plasma cell dyscrasias. Br J Haematol. 2022 Nov;199(4):520–8. 10.1111/bjh.18434 DOI: https://doi.org/10.1111/bjh.18434
  22. Zaleska, J.; Kwasnik, P.; Paziewska, M.; Purkot, J.; Szabelak, A.; Jurek, M.; Masny, N.; Dziatkiewicz, I.; Pronobis–Szczylik, B.; Piebiak, A.; et al. Response to Anti–SARS–CoV–2 MRNA Vaccines in Multiple Myeloma and Chronic Lymphocytic Leukemia Patients. International Journal of Cancer n/a, doi:10.1002/ijc.34209. DOI: https://doi.org/10.1002/ijc.34209
  23. Ramasamy K, Sadler R, Jeans S, Weeden P, Varghese S, Turner A, et al. Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T-cell response. Br J Haematol. 2022 May;197(3):293–301. 10.1111/bjh.18066 DOI: https://doi.org/10.1111/bjh.18066
  24. Marasco V, Carniti C, Guidetti A, Farina L, Magni M, Miceli R, et al. T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies. Br J Haematol. 2022 Feb;196(3):548–58. 10.1111/bjh.17877 DOI: https://doi.org/10.1111/bjh.17877
  25. Rouhani SJ, Yu J, Olson D, Zha Y, Pezeshk A, Cabanov A, et al. Antibody and T cell responses to COVID-19 vaccination in patients receiving anticancer therapies. J Immunother Cancer. 2022 Jun;10(6):e004766. 10.1136/jitc–2022–004766 10.1136/jitc-2022-004766 DOI: https://doi.org/10.1136/jitc-2022-004766
  26. Enßle JC, Campe J, Schwenger A, Wiercinska E, Hellstern H, Dürrwald R, et al. Severe impairment of T-cell responses to BNT162b2 immunization in patients with multiple myeloma. Blood. 2022 Jan;139(1):137–42. 10.1182/blood.2021013429 DOI: https://doi.org/10.1182/blood.2021013429
  27. Aleman A, Upadhyaya B, Tuballes K, Kappes K, Gleason CR, Beach K, et al.; PVI/Seronet Study Group. Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma. Cancer Cell. 2021 Nov;39(11):1442–4. 10.1016/j.ccell.2021.09.015 DOI: https://doi.org/10.1016/j.ccell.2021.09.015
  28. Wang L, Berger NA, Xu R. Risks of SARS-CoV-2 Breakthrough Infection and Hospitalization in Fully Vaccinated Patients With Multiple Myeloma. JAMA Netw Open. 2021 Nov;4(11):e2137575. 10.1001/jamanetworkopen.2021.37575 DOI: https://doi.org/10.1001/jamanetworkopen.2021.37575
  29. Wang L, Kaelber DC, Xu R, Berger NA. COVID-19 breakthrough infections, hospitalizations and mortality in fully vaccinated patients with hematologic malignancies: A clarion call for maintaining mitigation and ramping-up research. Blood Rev. 2022 Jul;54:100931. 10.1016/j.blre.2022.100931 DOI: https://doi.org/10.1016/j.blre.2022.100931
  30. Pinato DJ, Aguilar-Company J, Ferrante D, Hanbury G, Bower M, Salazar R, et al.; OnCovid study group. Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vaccinated and unvaccinated patients with cancer in Europe: results from the retrospective, multicentre, OnCovid registry study. Lancet Oncol. 2022 Jul;23(7):865–75. 10.1016/S1470–2045(22)00273–X 10.1016/S1470-2045(22)00273-X
  31. Terpos E, Rajkumar SV, Leung N. Neutralizing Antibody Testing in Patients With Multiple Myeloma Following COVID-19 Vaccination. JAMA Oncol. 2022 Feb;8(2):201–2. 10.1001/jamaoncol.2021.5942 DOI: https://doi.org/10.1001/jamaoncol.2021.5942
  32. Federal Vaccination Commission (FVC/EKIF/CFV); Swiss Society of Infectious Diseases (SSI/SGINF) Position Paper on the Use of Monoclonal Antibodies against SARS–CoV–2 as Passive Immunisation Treatments in Severely Immunocompromised Persons in Switzerland.
  33. Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, et al.; PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022 Jun;386(23):2188–200. 10.1056/NEJMoa2116620 DOI: https://doi.org/10.1056/NEJMoa2116620
  34. Nguyen Y, Flahault A, Chavarot N, Melenotte C, Cheminant M, Deschamps P, et al.; AP-HP-Centre Monoclonal Antibodies Working Group. Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients. Clin Microbiol Infect. 2022 Dec;28(12):1654.e1–4. 10.1016/j.cmi.2022.07.015 DOI: https://doi.org/10.1016/j.cmi.2022.07.015

Most read articles by the same author(s)

1 2 > >>