Immune dysfunction prior to and during vaccination in multiple myeloma: a case study based on COVID-19.
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
10 Jul 2024
10 Jul 2024
Historique:
received:
26
03
2024
accepted:
20
06
2024
revised:
18
06
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
10
7
2024
Statut:
epublish
Résumé
Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM (n = 28) and B-cell chronic lymphoproliferative disorders (n = 53) vs. health care practitioners (n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4
Identifiants
pubmed: 38987557
doi: 10.1038/s41408-024-01089-5
pii: 10.1038/s41408-024-01089-5
doi:
Substances chimiques
COVID-19 Vaccines
0
Antibodies, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111Investigateurs
Jesus F San Miguel
(JF)
Informations de copyright
© 2024. The Author(s).
Références
Blimark C, Holmberg E, Mellqvist UH, Landgren O, Bjorkholm M, Hultcrantz M, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015;100:107–13.
pubmed: 25344526
pmcid: 4281323
doi: 10.3324/haematol.2014.107714
John L, Miah K, Benner A, Mai EK, Kriegsmann K, Hundemer M, et al. Impact of novel agent therapies on immune cell subsets and infectious complications in patients with relapsed/refractory multiple myeloma. Front Oncol. 2023;13:1078725.
pubmed: 37152008
pmcid: 10160457
doi: 10.3389/fonc.2023.1078725
Holstein SA, Grant SJ, Wildes TM. Chimeric antigen receptor T-cell and bispecific antibody therapy in multiple myeloma: moving into the future. J Clin Oncol. 2023;41:4416–29.
pubmed: 37471687
doi: 10.1200/JCO.23.00512
Lancman G, Parsa K, Kotlarz K, Avery L, Lurie A, Lieberman-Cribbin A, et al. IVIg use associated with ten-fold reduction of serious infections in multiple myeloma patients treated with anti-BCMA bispecific antibodies. Blood Cancer Discov. 2023;4:440–51.
pubmed: 37769148
pmcid: 10618720
doi: 10.1158/2643-3230.BCD-23-0049
Chari A, Samur MK, Martinez-Lopez J, Cook G, Biran N, Yong K, et al. Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set. Blood. 2020;136:3033–40.
pubmed: 33367546
pmcid: 7759145
doi: 10.1182/blood.2020008150
Martínez-López J, Mateos MV, Encinas C, Sureda A, Hernández-Rivas JÁ, Lopez de la Guía A, et al. Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality. Blood Cancer J. 2020;10:103.
pubmed: 33077708
pmcid: 7570395
doi: 10.1038/s41408-020-00372-5
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603–15.
pubmed: 33301246
doi: 10.1056/NEJMoa2034577
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384:403–16.
pubmed: 33378609
doi: 10.1056/NEJMoa2035389
Piñana JL, Vazquez L, Calabuig M, López-Corral L, Martin-Martin G, Villalon L, et al. One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients. Blood Cancer J. 2023;13:8.
pubmed: 36599843
pmcid: 9812742
doi: 10.1038/s41408-022-00778-3
Chuleerarux N, Manothummetha K, Moonla C, Sanguankeo A, Kates OS, Hirankarn N, et al. Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis. Blood Adv. 2022;6:6198–207.
pubmed: 36538342
pmcid: 9561400
doi: 10.1182/bloodadvances.2022008530
Stampfer SD, Bujarski S, Goldwater MS, Jew S, Regidor B, Chen H, et al. Loss of anti-spike antibodies following mRNA vaccination for COVID-19 among patients with multiple myeloma. Cancer Rep. 2023;6:e1803.
doi: 10.1002/cnr2.1803
Terpos E, Musto P, Engelhardt M, Delforge M, Cook G, Gay F, et al. Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN). Leukemia. 2023;37:1175–85.
pubmed: 37142661
pmcid: 10157596
doi: 10.1038/s41375-023-01920-1
Starr TN, Czudnochowski N, Liu Z, Zatta F, Park YJ, Addetia A, et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature. 2021;597:97–102.
pubmed: 34261126
pmcid: 9282883
doi: 10.1038/s41586-021-03807-6
Dhodapkar MV. The immune system in multiple myeloma and precursor states: lessons and implications for immunotherapy and interception. Am J Hematol. 2023;98:S4–12.
pubmed: 36194782
doi: 10.1002/ajh.26752
Zavidij O, Haradhvala NJ, Mouhieddine TH, Sklavenitis-Pistofidis R, Cai S, Reidy M, et al. Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma. Nat Cancer. 2020;1:493–506.
pubmed: 33409501
pmcid: 7785110
doi: 10.1038/s43018-020-0053-3
Liu R, Gao Q, Foltz SM, Fowles JS, Yao L, Wang JT, et al. Co-evolution of tumor and immune cells during progression of multiple myeloma. Nat Commun. 2021;12:1–18.
Botta C, Perez C, Larrayoz M, Puig N, Cedena MT, Termini R, et al. Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance. Nat Commun. 2023;14:1–15.
doi: 10.1038/s41467-023-41562-6
Luoma S, Sergeev P, Javarappa KK, Öhman TJ, Varjosalo M, Säily M, et al. Deep immune profiling of multiple myeloma at diagnosis and under lenalidomide maintenance therapy. Cancers (Basel). 2023;15:2604.
pubmed: 37174069
doi: 10.3390/cancers15092604
Coffey DG, Maura F, Gonzalez-Kozlova E, Diaz-Mejia JJ, Luo P, Zhang Y, et al. Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma. Nat Commun. 2023;14:1–12.
doi: 10.1038/s41467-023-40966-8
Sklavenitis-Pistofidis R, Aranha MP, Redd RA, Trippa L, Getz G, Ghobrial IM, et al. Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma. Cancer Cell. 2022;40:1358–1373.e8.
pubmed: 36379208
pmcid: 10019228
doi: 10.1016/j.ccell.2022.10.017
Papadimitriou K, Ntanasis-Stathopoulos I, Tsakirakis N, Gavriatopoulou M, Kostopoulos I, Kastritis E, et al. Peripheral blood immune profiling of multiple myeloma patients at diagnosis: correlations with circulating plasma cells. Hematol Transfus Cell Ther. 2020;42:24.
doi: 10.1016/j.htct.2020.09.045
Raje NS, Anaissie E, Kumar SK, Lonial S, Martin T, Gertz MA, et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol. 2022;9:e143–61.
pubmed: 35114152
doi: 10.1016/S2352-3026(21)00283-0
Romano A, Cerchione C, Conticello C, Filetti S, Bulla A, Chiarenza A, et al. Reduced absolute count of monocytes in patients carrying hematological neoplasms and SARS-CoV2 infection. Cancers (Basel). 2022;14:1173.
pubmed: 35267478
doi: 10.3390/cancers14051173
Pagano L, Salmanton-García J, Marchesi F, Busca A, Corradini P, Hoenigl M, et al. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA). J Hematol Oncol. 2021;14:1–15.
doi: 10.1186/s13045-021-01177-0
Martín-Sánchez E, Garcés JJ, Maia C, Inogés S, López-Díaz de Cerio A, Carmona-Torre F, et al. Immunological biomarkers of fatal COVID-19: a study of 868 patients. Front Immunol. 2021;12:659018.
pubmed: 34012444
pmcid: 8126711
doi: 10.3389/fimmu.2021.659018
Rébillard RM, Charabati M, Grasmuck C, Filali-Mouhim A, Tastet O, Brassard N, et al. Identification of SARS-CoV-2–specific immune alterations in acutely ill patients. J Clin Investig. 2021;131:e145853.
pubmed: 33635833
pmcid: 8262478
doi: 10.1172/JCI145853
Reynolds G, Cliff ERS, Mohyuddin GR, Popat R, Midha S, Hing MNL, et al. Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis. Blood Adv. 2023;7:5898–903.
pubmed: 37467036
pmcid: 10558589
doi: 10.1182/bloodadvances.2023010539
Azeem MI, Nooka AK, Shanmugasundaram U, Cheedarla N, Potdar S, Manalo RJ, et al. Impaired SARS-CoV-2 variant neutralization and CD8+ T cell responses following 3 doses of mRNA vaccines in myeloma: correlation with breakthrough infections. Blood Cancer Discov. 2023;4:106–17.
pubmed: 36511813
doi: 10.1158/2643-3230.BCD-22-0173
Nooka AK, Shanmugasundaram U, Cheedarla N, Verkerke H, Edara VV, Valanparambil R, et al. Determinants of neutralizing antibody response after SARS CoV-2 vaccination in patients with myeloma. J Clin Oncol. 2022;40:3057–64.
pubmed: 35259002
pmcid: 9462534
doi: 10.1200/JCO.21.02257
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;139:1409–12.
pubmed: 34986251
pmcid: 8736278
doi: 10.1182/blood.2021014989
Fendler A, Shepherd STC, Au L, Wilkinson KA, Wu M, Schmitt AM, et al. Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer. Cancer Cell. 2022;40:114–6.
pubmed: 34968417
doi: 10.1016/j.ccell.2021.12.013
Keppler-Hafkemeyer A, Greil C, Wratil PR, Shoumariyeh K, Stern M, Hafkemeyer A, et al. Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma. Nat Cancer. 2023;4:81–95.
pubmed: 36543907
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;27:1280–9.
pubmed: 34017137
pmcid: 8291091
doi: 10.1038/s41591-021-01386-7
Fendler A, Shepherd STC, Au L, Wilkinson KA, Wu M, Byrne F, et al. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study. Nat Cancer. 2021;2:1305–20.
pubmed: 35121899
doi: 10.1038/s43018-021-00274-w
Engelmann R, Jaekel N, Jotschke S, Ludwig-Kraus B, Kraus FB, Kumari N, et al. Vector-based SARS-CoV-2 vaccination is associated with improved T-cell responses in hematological neoplasia. Blood Adv. 2023;7:3403–15.
pubmed: 36947191
pmcid: 10065874
doi: 10.1182/bloodadvances.2022009054
Nguyen THO, Rowntree LC, Allen LF, Chua BY, Kedzierski L, Lim C, et al. Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells. Cell Rep Med. 2023;4:101017.
pubmed: 37030296
pmcid: 10040362
doi: 10.1016/j.xcrm.2023.101017
Berger M, Figari O, Bruno B, Raiola A, Dominietto A, Fiorone M, et al. Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant-related mortality. Bone Marrow Transpl. 2008;41:55–62.
doi: 10.1038/sj.bmt.1705870
Talmadge JE. Lymphocyte subset recovery following allogeneic bone marrow transplantation: CD4(+)-cell count and transplant-related mortality. Bone Marrow Transpl. 2008;41:19–21.
doi: 10.1038/sj.bmt.1705871
Kim DH, Sohn SK, Won DI, Lee NY, Suh JS, Lee KB. Rapid helper T-cell recovery above 200 × 106/l at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation. Bone Marrow Transpl. 2006;37:1119–28.
Twumasi C, Moore S, Sadler R, Jeans S, Varghese S, Turner A. et al. Determinants of durable humoral and T cell immunity in myeloma patients following COVID-19 vaccination. Eur J Haematol. 2023;112:547–53.
pubmed: 38116695
doi: 10.1111/ejh.14143
Aleman A, van Kesteren M, Zajdman AK, Srivastava K, Cognigni C, Mischka J, et al. Cellular mechanisms associated with sub-optimal immune responses to SARS-CoV-2 bivalent booster vaccination in patients with Multiple Myeloma. eBioMedicine. 2023;98:104886.
pubmed: 37995467
pmcid: 10708991
doi: 10.1016/j.ebiom.2023.104886
Amarin JZ, Dulek DE, Simmons J, Hayek H, Chappell JD, Nochowicz CH. et al. Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients. Blood Adv. 2024;8:1880–92.
pubmed: 38386973
pmcid: 11007439
doi: 10.1182/bloodadvances.2023012118
Kalina T, Flores-Montero J, Van Der Velden VHJ, Martin-Ayuso M, Böttcher S, Ritgen M, et al. EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols. Leukemia. 2012;26:1986–2010.
pubmed: 22948490
pmcid: 3437409
doi: 10.1038/leu.2012.122
Botta C, Maia C, Garcés JJ, Termini R, Perez C, Manrique I, et al. FlowCT for the analysis of large immunophenotypic data sets and biomarker discovery in cancer immunology. Blood Adv. 2022;6:690–703.
pubmed: 34587246
pmcid: 8791585
doi: 10.1182/bloodadvances.2021005198
Cáceres-Martell Y, Fernández-Soto D, Campos-Silva C, García-Cuesta EM, Casasnovas JM, Navas-Herrera D, et al. Single-reaction multi-antigen serological test for comprehensive evaluation of SARS-CoV-2 patients by flow cytometry. Eur J Immunol. 2021;51:2633–40.
pubmed: 34358329
pmcid: 8420214
doi: 10.1002/eji.202149319
Chen KY, Liu J, Ren EC. Structural and functional distinctiveness of HLA-A2 allelic variants. Immunol Res. 2012;53:182–90.
pubmed: 22434516
doi: 10.1007/s12026-012-8295-5