COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

Tsutsumi,Yutaka; Ito,Shinichi; Horikita,Fuka; Moriki,Asako; Teshima,Takanori

doi:10.3892/mco.2023.2692

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

Authors:
- Yutaka Tsutsumi
- Shinichi Ito
- Fuka Horikita
- Asako Moriki
- Takanori Teshima
View Affiliations

Affiliations: Department of Hematology, Hakodate Municipal Hospital, Minato‑cho, Hakodate, Hokkaido 041‑8680, Japan, Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060‑8638, Japan
Published online on: October 18, 2023 https://doi.org/10.3892/mco.2023.2692
Article Number: 96
Copyright: © Tsutsumi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Most hematologic diseases are immunosuppressed, either by the disease itself or by treatment. As such, the implementation of vaccination is largely at the discretion of the attending physician. In this context, an objective measure is needed, therefore the index of vaccination against coronavirus disease 2019 (COVID‑19) in B‑cell lymphomas treated with antibody therapy against CD20 (including after the completion of therapy) was examined. A total of 40 patients with B‑cell lymphoma during or after antibody therapy against CD20 were vaccinated twice with the BNT162b2 messenger RNA (mRNA) COVID‑19 vaccine (Pfizer, Inc. and BioNTech SE.) at 3‑week intervals and then again six months later with the same vaccine or mRNA‑1273 (Moderna, Inc.). Antibody testing was conducted ~1 month after the third vaccination. Analysis was performed using the antibody titers to the anti‑spike immunoglobulin assay, with a titer of 0.8 U/ml or higher (considered positive) and a titer of 264 U/ml or higher (considered the value at which the efficacy of the vaccine can be fully expected). Significant factors of antibody acquisition were identified when i) antibody titers were 0.8 U/ml or higher (CD4 ≥400/µl), ii) no anti‑CD20 antibody maintenance therapy was undertaken (CD19 ≥100/µl), iii) patients were not on treatment (CD4 ≥400/µl), or 4) at least six months had passed since treatment ended (CD19 ≥100/µl). When antibody titers were 264 U/ml or higher, the treatment method, the stage of the primary disease and other factors related to the condition treatment method of the patient were relevant. When these were analyzed by multivariate analysis, the significant factor when antibody titers were set to 0.8 U/ml was CD19 ≥100/µl. In contrast, when setting them to 264 U/ml or higher, CD4 ≥400/µl was not significant, but there was a tendency for it to be related. The findings of the present study on vaccine‑induced antibody acquisition in patients with B‑cell lymphoma indicated that it is desirable to have a CD19 titer of at least 100/µl and a CD4 titer of at least 400/µl (both conditions should be met), and that no maintenance therapy with anti‑CD20 antibody should be administered for at least six months after the last treatment or completion of the treatment. Interestingly, when the criteria for antibody titers were compared between 0.8 U/ml, where antibody titer is detected, and 264 U/ml, where vaccine efficacy is expected, several key factors were different. It is possible that these key factors may change depending on the antibody titer used as a criterion.

View Figures

View References

1	Pinana JL, Martino R, Garcia-Garcia I, Parody R, Morales MD, Benzo G, Gómez-Catalan I, Coll R, De La Fuente I, Luna A, et al: Risk factors and outcome of COVID-19 inpatients with hematological malignancies. Exp Hematol Oncol. 9(21)2020.PubMed/NCBI View Article : Google Scholar
2	Vijenthira A, Gong IY, Fox TA, Booth S, Cook G, Fattizzo B, Martin-Moro F, Razanamahery J, Riches JC, Zwicker J, et al: Outcomes of patients with hematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377 patients. Blood. 136:2881–2892. 2020.PubMed/NCBI View Article : Google Scholar
3	Asch DA, Sheils NE, Islam MN, Chen Y, Werner RM, Buresh J and Doshi JA: Variation in US hospital mortality rates for patients admitted with COVID-19 during the first 6 months of the pandemic. JAMA Intern Med. 181:471–478. 2021.PubMed/NCBI View Article : Google Scholar
4	Sun C, Pleyer C and Wiestner A: COVID-19 vaccines for patients with hematological conditions. Lancet Haematol. 8:e312–e314. 2021.PubMed/NCBI View Article : Google Scholar
5	Riester E, Findeisen P, Hegel JK, Kabesch M, Ambrosch A, Rank CM, Pessl F, Laengin T and Niederhauser C: Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay. J Virol Methods. 297(114271)2021.PubMed/NCBI View Article : Google Scholar
6	Feng S, Phillips DJ, White T, Sayal H, Aley PK, Bibi S, Dold C, Fuskova M, Gilbert SC, Hirsch I, et al: Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nat Med. 27:2032–2040. 2021.PubMed/NCBI View Article : Google Scholar
7	Perkmann T, Perkmann-Nagele N, Koller T, Mucher P, Radakovics A, Marculescu R, Wolzt M, Wagner OF, Binder CJ and Haslacher H: Anti-Spike protein assays to determine SARS-CoV-2 antibody levels: A head-to-head comparison of five quantitative assays. Microbiol Spectr. 9(e0024721)2021.PubMed/NCBI View Article : Google Scholar
8	Perry C, Luttwak E, Balaban R, Shefer G, Morales MM, Aharon A, Tabib Y, Cohen C, Benyamini N, Beyar-Katz O, et al: Efficacy of the BNT162b2 mRNA COVID-19 vaccine patients with B-cell non-Hodgkin lymphoma. Blood Adv. 5:3053–3061. 2021.PubMed/NCBI View Article : Google Scholar
9	Re D, Barriere J, Chamorey E, Delforge M, Gastaud L, Petit E, Chaminade A, Verrriere B and Peyrade F: Low rate of seroconversion after m RNA anti-SARS-CoV-2 vaccination in patients with hematological malignancies. Leuk Lymphoma. 62:3308–3310. 2021.PubMed/NCBI View Article : Google Scholar
10	Avivi I, Luttwak E, Saiang E, Halperin T, Haberman S, Saring A, Levi S, Aharon A, Herishanu Y and Perry C: BNT-162b2 m RNA COVID-19 vaccine booster induces seroconversion in patients with B-cell non-Hodgkin lymphoma who failed to respond to two prior vaccine doses. Br J Haematol. 196:1329–1333. 2022.PubMed/NCBI View Article : Google Scholar
11	Moor MB, Suter-Riniker F, Horn MP, Aeberli D, Amsler J, Möller B, Njue LM, Medri C, Angelillo-Scherrer A, Borradori L, et al: Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): An investigator-initiated, single-centre, open-label study. Lancet Rheumatol. 3:e789–e797. 2021.PubMed/NCBI View Article : Google Scholar
12	Schubert L, Koblischke M, Schneider L, Porpaczy E, Winkler F, Jaeger U, Blüml S, Haslacher H, Burgmann H, Aberle JH, et al: Immunogenicity of COVID-19 vaccinations in hematological patients: 6-month follow-up and evaluation of a 3rd vaccination. Cancers (Basel). 14(1962)2022.PubMed/NCBI View Article : Google Scholar
13	Tsushima T, Terao T, Narita K, Fukumoto A, Ikeda D, Kamura Y, Kuzume A, Tabata R, Miura D, Takeuchi M and Matsue K: Antibody response to COVID-19 vaccine in 130 recipients of hematopoietic stem cell transplantation. Int J Hematol. 115:611–615. 2022.PubMed/NCBI View Article : Google Scholar
14	Narita K, Nakaji S, Tabata R, Terao T, Kuzume A, Tsushima T, Ikeda D, Fukumoto A, Miura D, Takeuchi M, et al: Antibody response to COVID-19 vaccination in patients with lymphoma. Int J Hematol. 115:728–736. 2022.PubMed/NCBI View Article : Google Scholar
15	Antolí A, Rocamora-Blanch G, Framil M, Mas-Bosch V, Navarro S, Bermudez C, Martinez-Yelamos S, Dopico E, Calatayud L, Garcia-Muñoz N, et al: Evaluation of Humoral and Cellular Immune Responses to the SARS-CoV-2 Vaccine in Patients With Common Variable Immunodeficiency Phenotype and Patient Receiving B-Cell Depletion Therapy. Front Immunol. 13(895209)2022.PubMed/NCBI View Article : Google Scholar
16	Ram R, Hagin D, Kikozashvilli N, Freund T, Amit O, Bar-On Y, Beyar-Katz O, Shefer G, Moshiashvili MM, Karni C, et al: Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients after allogeneic HCT or CD19-based CART therapy-A single-center prospective cohort study. Transplant Cell Ther. 27:788–794. 2021.PubMed/NCBI View Article : Google Scholar
17	Jarisch A, Wiercinska E, Huenecke S, Bremm M, Cappel C, Hauler J, Rettinger E, Soerensen J, Hellstern H, Klusmann JH, et al: Immune Responses to SARS-CoV-2 vaccination in young patients with Anti-CD19 chimeric antigen receptor T cell-induced B Cell Aplasia. Transplant Cell Ther. 28:366.e1–366.e7. 2022.PubMed/NCBI View Article : Google Scholar
18	Baron F, Canti L, Ariën KK, Kemlin D, Desombere I, Gerbaux M, Pannus P, Beguin Y, Marchant A and Humblet-Baron S: . Insights from early clinical trials assessing response to mRNA SARS-CoV-2 vaccination in immunocompromised patients. Front Immunol. 13(827242)2022.PubMed/NCBI View Article : Google Scholar
19	Duni A, Markopoulos GS, Mallioras I, Pappas H, Pappas E, Koutlas V, Tzalavra E, Baxevanos G, Priska S, Gartzonika K, et al: The humoral immune response to BNT162b2 vaccine is associated with circulating CD19+ B lymphocytes and the naïve CD45RA to Memory CD45RO CD4+ T helper cells ratio in hemodialysis patients and kidney transplant recipients. Front Immunol. 12(760249)2021.PubMed/NCBI View Article : Google Scholar
20	Ishio T, Tsukamoto S, Yokoyama E, Izumiyama K, Saito M, Muraki H, Kobayashi M, Mori A, Morioka M and Kondo T: Anti-CD20 antibodies and bendamustine attenuate humoral immunity to COVID-19 vaccination in patients with B-cell non-Hodgkin lymphoma. Ann Hematol. 102:1421–1431. 2023.PubMed/NCBI View Article : Google Scholar
21	Liebers N, Speer C, Benning L, Bruch PM, Kraemer I, Meissner J, Schnitzler P, Kräusslich HG, Dreger P, Mueller-Tidow C, et al: Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients. Blood. 139:142–147. 2022.PubMed/NCBI View Article : Google Scholar
22	Nishikubo M, Shimomura Y, Yamamoto R, Yoshioka S, Maruoka H, Nasu S, Nishioka T, Sakizono K, Mitsuyuki S, Kubo T, et al: Humoral and cellular responses after COVID-19 booster vaccination in patients recently treated with anti-CD20 antibodies. Blood Cancer J. 13(17)2023.PubMed/NCBI View Article : Google Scholar