Clinical and Experimental Vaccine Research

The Korean Vaccine Society (대한백신학회)
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Serological response 5 months after the BNT162b2 COVID-19 vaccination in patients with various hematological disorders in Japan

  • Yoshiaki Marumo (Department of Clinical Oncology, Nagoya Memorial Hospital) ;
  • Takashi Yoshida (Department of Clinical Oncology, Nagoya Memorial Hospital) ;
  • Yuki Furukawa (Department of Clinical Oncology, Nagoya Memorial Hospital) ;
  • Kenji Ina (Department of Clinical Oncology, Nagoya Memorial Hospital) ;
  • Ayumi Kamiya (Department of Clinical Oncology, Nagoya Memorial Hospital) ;
  • Takae Kataoka (Department of Clinical Oncology, Nagoya Memorial Hospital) ;
  • Satoshi Kayukawa (Department of Clinical Oncology, Nagoya Memorial Hospital)
  • Received : 2023.08.03
  • Accepted : 2023.10.14
  • Published : 2023.10.31
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Abstract

Purpose: Patients with hematological malignancies are at an increased risk of severe infection with coronavirus disease 2019 (COVID-19). However, developing an adequate immune response after vaccination is difficult, especially in patients with lymphoid neoplasms. Since the long-term effects of the BNT162b2 vaccine are unclear, the humoral immune response 5 months after the two vaccinations in patients with hematological disorders was analyzed. Materials and Methods: Samples were collected from 96 patients vaccinated twice with BNT162b2 and treated with at least one line of an antitumor or immunosuppressive drug in our hospital from November 2021 to February 2022. Serum anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) spike (S) antibody titers were analyzed. Patients were age- and sex-matched using propensity matching and compared with a healthy control group. Patients with serum anti-SARS-CoV-2 S antibodies were defined as 'responder' if >50 U/mL. The patients had B-cell non-Hodgkin lymphoma (B-NHL), multiple myeloma, chronic myeloid leukemia, etc. Results: Patients had significantly low antibody levels (median, 55.3 U/mL vs. 809.8 U/mL; p<0.001) and a significantly low response rate (p<0.001). Multivariate analysis showed that patients with B-NHL, aged >72 years, were associated with a low response to vaccination. There were no significant differences between patients with chronic myeloid leukemia and healthy controls. Conclusion: Our study shows that patients with hematological disorders are at risk of developing severe COVID-19 infections because of low responsiveness to vaccination. Moreover, the rate of antibody positivity differed between the disease groups. Further studies are warranted to determine an appropriate preventive method for these patients, especially those with B-NHL.

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References

  1. World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19: 11 March 2020 [Internet]. Geneva: World Health Organization; 2020 [cited 2023 May 15]. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 
  2. Pagano L, Salmanton-Garcia J, Marchesi F, et al. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA). J Hematol Oncol 2021;14:168. 
  3. Vijenthira A, Gong IY, Fox TA, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood 2020;136:2881-92. 
  4. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med 2020;383:2603-15. 
  5. Pharmaceutical and Medical Devices Agency. Special approval for emergency on first COVID-19 vaccine in Japan [Internet]. Tokyo: Pharmaceutical and Medical Devices Agency; 2021 [cited 2022 Dec 5]. https://www.pmda.go.jp/english/about-pmda/0003.pdf 
  6. Painter MM, Mathew D, Goel RR, et al. Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination. Immunity 2021;54:2133-42. 
  7. Herzog Tzarfati K, Gutwein O, Apel A, et al. BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies. Am J Hematol 2021;96:1195-203. 
  8. Harvey RA, Rassen JA, Kabelac CA, et al. Association of SARS-CoV-2 seropositive antibody test with risk of future infection. JAMA Intern Med 2021;181:672-9. 
  9. Okamoto A, Fujigaki H, Iriyama C, et al. CD19-positive lymphocyte count is critical for acquisition of anti-SARS-CoV-2 IgG after vaccination in B-cell lymphoma. Blood Adv 2022;6:3230-3. 
  10. Bitoun S, Henry J, Vauloup-Fellous C, et al. Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls. J Hematol Oncol 2021;14:166. 
  11. Petzer V, Steiner N, Angelova-Unterberger O, et al. Serologic responses to COVID-19 vaccines in hematological patients are predominantly impaired in lymphoid but not in myeloid malignancies. Hemasphere 2022;6:e686. 
  12. Kayukawa S, Nanya K, Morita M, Ina K, Ota Y, Hasegawa S. Spike antibody titers evaluation after a 2-dose regimen of BNT162b2 vaccination in healthcare workers previously infected with SARS-CoV-2. Microbiol Spectr 2021;9:e0103621. 
  13. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013;48:452-8. 
  14. Parthymou A, Habeos EE, Habeos GI, et al. Factors associated with anti-SARS-CoV-2 antibody titres 3 months post-vaccination with the second dose of BNT162b2 vaccine: a longitudinal observational cohort study in western Greece. BMJ Open 2022;12:e057084. 
  15. Takahashi W, Mizuno T, Hara K, et al. Association of systemic adverse reactions and serum SARS-CoV-2 spike protein antibody levels after administration of BNT162b2 mRNA COVID-19 vaccine. Intern Med 2022;61:3205-10. 
  16. Maneikis K, Sablauskas K, Ringeleviciute U, et al. Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study. Lancet Haematol 2021;8:e583-92. 
  17. Gur I, Giladi A, Isenberg YN, Neuberger A, Stern A. COVID-19 in patients with hematologic malignancies: clinical manifestations, persistence, and immune response. Acta Haematol 2022;145:297-309. 
  18. Katagiri S, Akahane D, Otsuki S, et al. Tyrosine kinase inhibitors do not promote a decrease in SARS-CoV-2 anti-spike IgG after BNT162b2 vaccination in chronic myeloid leukemia: a prospective observational study. Vaccines (Basel) 2022;10:1404. 
  19. Haggenburg S, Hofsink Q, Lissenberg-Witte BI, et al. Antibody response in immunocompromised patients with hematologic cancers who received a 3-dose mRNA-1273 vaccination schedule for COVID-19. JAMA Oncol 2022;8:1477-83. 
  20. Anolik JH, Friedberg JW, Zheng B, et al. B cell reconstitution after rituximab treatment of lymphoma recapitulates B cell ontogeny. Clin Immunol 2007;122:139-45. 
  21. Susol O, Hajkova B, Zelena H, Hajek R. Third dose of COVID-19 vaccine restores immune response in patients with haematological malignancies after loss of protective antibody titres. Br J Haematol 2022;197:302-5.