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

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2022 Sep 15

PMID 36105747

Authors

Paola Storti

Valentina Marchica

Rosanna Vescovini

Valentina Franceschi

Luca Russo

Laura Notarfranchi

Vincenzo Raimondi

Denise Toscani

Jessica Burroughs Garcia

Federica Costa

Benedetta Dalla Palma

Nicolas Thomas Iannozzi

Gabriella Sammarelli

Gaetano Donofrio

Nicola Giuliani

Affiliations

Soon will be listed here.

Abstract

The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of the spike variants, including Omicron, are still unclear in patients with multiple myeloma (MM) and those with pre-malignant monoclonal gammopathies. In this study, involving 40 patients, we found that MM patients with relapsed-refractory disease (MMR) had reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 vaccination. The five analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and smoldering MM. Moreover, lower spike-specific IL-2-producing CD4 T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing CD8 T cells were found in MM patients as compared to patients with monoclonal gammopathy of undetermined significance. We found that a heterologous booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. However, in MMR patients, Omicron retained a negative impact on neutralizing ability, suggesting further approaches to potentiating the effectiveness of SARS-CoV-2 vaccination in these patients.

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References

Sette A, Crotty S . Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021; 184(4):861-880. PMC: 7803150. DOI: 10.1016/j.cell.2021.01.007. View

Hoffmann M, Kruger N, Schulz S, Cossmann A, Rocha C, Kempf A . The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic. Cell. 2022; 185(3):447-456.e11. PMC: 8702401. DOI: 10.1016/j.cell.2021.12.032. View

Cameroni E, Bowen J, Rosen L, Saliba C, Zepeda S, Culap K . Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature. 2022; 602(7898):664-670. PMC: 9531318. DOI: 10.1038/s41586-021-04386-2. View

Pimpinelli F, Marchesi F, Piaggio G, Giannarelli D, Papa E, Falcucci P . Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution. J Hematol Oncol. 2021; 14(1):81. PMC: 8128283. DOI: 10.1186/s13045-021-01090-6. View

Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, Briasoulis A, Gumeni S, Malandrakis P . Booster BNT162b2 optimizes SARS-CoV-2 humoral response in patients with myeloma: the negative effect of anti-BCMA therapy. Blood. 2022; 139(9):1409-1412. PMC: 8736278. DOI: 10.1182/blood.2021014989. View

Konishi Y, Sklavenitis-Pistofidis R, Yue H, Ferrari F, Redd R, Lightbody E . Attenuated response to SARS-CoV-2 vaccine in patients with asymptomatic precursor stages of multiple myeloma and Waldenstrom macroglobulinemia. Cancer Cell. 2021; 40(1):6-8. PMC: 8654583. DOI: 10.1016/j.ccell.2021.12.003. View

Zhou D, Dejnirattisai W, Supasa P, Liu C, Mentzer A, Ginn H . Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Cell. 2021; 184(9):2348-2361.e6. PMC: 7901269. DOI: 10.1016/j.cell.2021.02.037. View

Ho M, Goh C, Patel A, Staunton S, OConnor R, Godeau M . Role of the Bone Marrow Milieu in Multiple Myeloma Progression and Therapeutic Resistance. Clin Lymphoma Myeloma Leuk. 2020; 20(10):e752-e768. DOI: 10.1016/j.clml.2020.05.026. View

Fendler A, Shepherd S, Au L, Wu M, Harvey R, Schmitt A . Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer. Lancet. 2022; 399(10328):905-907. PMC: 8789238. DOI: 10.1016/S0140-6736(22)00147-7. View

10.

Mateos M, Kumar S, Dimopoulos M, Gonzalez-Calle V, Kastritis E, Hajek R . International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 2020; 10(10):102. PMC: 7567803. DOI: 10.1038/s41408-020-00366-3. View

11.

Bange E, Han N, Wileyto P, Kim J, Gouma S, Robinson J . CD8 T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat Med. 2021; 27(7):1280-1289. PMC: 8291091. DOI: 10.1038/s41591-021-01386-7. View

12.

Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin J, Olsson A . Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020; 183(1):158-168.e14. PMC: 7427556. DOI: 10.1016/j.cell.2020.08.017. View

13.

Stampfer S, Goldwater M, Jew S, Bujarski S, Regidor B, Daniely D . Response to mRNA vaccination for COVID-19 among patients with multiple myeloma. Leukemia. 2021; 35(12):3534-3541. PMC: 8320411. DOI: 10.1038/s41375-021-01354-7. View

14.

Grifoni A, Weiskopf D, Ramirez S, Mateus J, Dan J, Rydyznski Moderbacher C . Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; 181(7):1489-1501.e15. PMC: 7237901. DOI: 10.1016/j.cell.2020.05.015. View

15.

Ludwig H, Boccadoro M, Moreau P, San-Miguel J, Cavo M, Pawlyn C . Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network. Leukemia. 2020; 35(1):31-44. PMC: 7787974. DOI: 10.1038/s41375-020-01016-0. View

16.

Donofrio G, Franceschi V, Macchi F, Russo L, Rocci A, Marchica V . A Simplified SARS-CoV-2 Pseudovirus Neutralization Assay. Vaccines (Basel). 2021; 9(4). PMC: 8071407. DOI: 10.3390/vaccines9040389. View

17.

Rydyznski Moderbacher C, Ramirez S, Dan J, Grifoni A, Hastie K, Weiskopf D . Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell. 2020; 183(4):996-1012.e19. PMC: 7494270. DOI: 10.1016/j.cell.2020.09.038. View

18.

Martinez-Lopez J, Hernandez-Ibarburu G, Alonso R, Sanchez-Pina J, Zamanillo I, Lopez-Munoz N . Impact of COVID-19 in patients with multiple myeloma based on a global data network. Blood Cancer J. 2021; 11(12):198. PMC: 8661359. DOI: 10.1038/s41408-021-00588-z. View

19.

Naranbhai V, Nathan A, Kaseke C, Berrios C, Khatri A, Choi S . T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals. Cell. 2022; 185(6):1041-1051.e6. PMC: 8810349. DOI: 10.1016/j.cell.2022.01.029. View

20.

Bertoletti A, Bert N, Qui M, Tan A . SARS-CoV-2-specific T cells in infection and vaccination. Cell Mol Immunol. 2021; 18(10):2307-2312. PMC: 8408362. DOI: 10.1038/s41423-021-00743-3. View