{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:26:32Z","timestamp":1793499992285,"version":"4.5.0"},"reference-count":96,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,20]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Immunotherapy has transformed the treatment landscape of multiple myeloma (MM), a hematological cancer predominantly affecting older individuals. Yet, whether immune aging, shaped by intrinsic aging processes, genetics, and external factors, affects treatment efficacy remains unclear. To address this, we investigated the influence of age on the immune system in patients with MM and explored whether immune aging associates with clinical outcomes in older patients. Using flow cytometry, we conducted high-dimensional profiling of T cells and natural killer cells in peripheral blood and bone marrow samples of 124 older (&amp;gt;65 years) and 145 younger (\u226465 years) patients with newly diagnosed MM (ages 34-92 years) enrolled in the HOVON-143 and CASSIOPEIA\/HOVON-131 trials. On average, older patients exhibited a more activated, differentiated, and senescent T-cell compartment than younger patients. Nonetheless, substantial interindividual variation in T-cell subset frequencies within both age groups indicated that calendar age inadequately reflects an individual\u2019s immune status. We therefore developed an immune clock on high-dimensional phenotypic T-cell data to quantify each patient\u2019s \u201cimmune age,\u201d revealing substantial variation in immune ages among patients of similar calendar age. Importantly, immune age appeared a stronger predictor of clinical outcomes than calendar age in older, nonfit patients with newly diagnosed MM receiving daratumumab-ixazomib-dexamethasone, even after adjusting for frailty and other established risk factors. Overall, these findings highlight immune age as a clinically relevant composite metric that better reflects a patient\u2019s immune status than their calendar age. Validating this methodology in other immunotherapy settings may improve our ability to predict immunotherapy efficacy in older patients with MM or other hematological cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025028587","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T20:54:57Z","timestamp":1755636897000},"page":"2517-2530","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":13,"title":["A T-cell\u2013based metric of immune age predicts outcomes in older patients with myeloma receiving daratumumab-based therapy"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-9257","authenticated-orcid":false,"given":"Wassilis S. C.","family":"Bruins","sequence":"first","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Febe","family":"Smits","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"},{"name":"3Department of Hematology, Haga Hospital, The Hague, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolien","family":"Duetz","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaz","family":"Groen","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0191-4343","authenticated-orcid":false,"given":"Charlotte L. B. M.","family":"Korst","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-1762","authenticated-orcid":false,"given":"A. Vera","family":"de Jonge","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie P. M.","family":"Verkleij","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3317-437X","authenticated-orcid":false,"given":"Rosa","family":"Rentenaar","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meliha","family":"Cosovic","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Eken","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inoka","family":"Twickler","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola M.","family":"Homan-Weert","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-2237","authenticated-orcid":false,"given":"Pieter","family":"Sonneveld","sequence":"additional","affiliation":[{"name":"4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"5Hematology Department, University Hospital H\u00f4tel-Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Claesen","sequence":"additional","affiliation":[{"name":"6Department of Epidemiology and Data Science, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels W. C. J.","family":"van de Donk","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5011-1820","authenticated-orcid":false,"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-7187","authenticated-orcid":false,"given":"Tuna","family":"Mutis","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"2Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2025112011214548000_bib1","unstructured":"SEER\n          . Cancer stat facts: myeloma. Accessed 9 February 2024. https:\/\/seer.cancer.gov\/statfacts\/html\/mulmy.html."},{"key":"2025112011214548000_bib2","doi-asserted-by":"crossref","first-page":"m3176","DOI":"10.1136\/bmj.m3176","article-title":"Emerging immunotherapies in multiple myeloma","volume":"370","author":"Shah","year":"2020","journal-title":"BMJ"},{"issue":"19","key":"2025112011214548000_bib3","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1056\/NEJMoa1114138","article-title":"Lenalidomide maintenance after stem-cell transplantation for multiple myeloma","volume":"366","author":"Attal","year":"2012","journal-title":"N Engl J Med"},{"issue":"1","key":"2025112011214548000_bib4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S1470-2045(18)30687-9","article-title":"Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial","volume":"20","author":"Jackson","year":"2019","journal-title":"Lancet Oncol"},{"issue":"11","key":"2025112011214548000_bib5","doi-asserted-by":"crossref","first-page":"E822","DOI":"10.1016\/S2352-3026(22)00290-3","article-title":"Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1\/2 trial","volume":"9","author":"Lonial","year":"2022","journal-title":"Lancet Haematol"},{"issue":"11","key":"2025112011214548000_bib6","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1056\/NEJMoa2303194","article-title":"Mezigdomide plus dexamethasone in relapsed and refractory multiple myeloma","volume":"389","author":"Richardson","year":"2023","journal-title":"N Engl J Med"},{"issue":"13","key":"2025112011214548000_bib7","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa1506348","article-title":"Targeting CD38 with daratumumab monotherapy in multiple myeloma","volume":"373","author":"Lokhorst","year":"2015","journal-title":"N Engl J Med"},{"issue":"22","key":"2025112011214548000_bib8","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1056\/NEJMoa1817249","article-title":"Daratumumab plus lenalidomide and dexamethasone for untreated myeloma","volume":"380","author":"Facon","year":"2019","journal-title":"N Engl J Med"},{"issue":"4","key":"2025112011214548000_bib9","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1056\/NEJMoa2312054","article-title":"Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma","volume":"390","author":"Sonneveld","year":"2024","journal-title":"N Engl J Med"},{"issue":"10214","key":"2025112011214548000_bib10","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(19)32556-5","article-title":"Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study","volume":"394","author":"Attal","year":"2019","journal-title":"Lancet"},{"issue":"2","key":"2025112011214548000_bib11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1470-2045(19)30788-0","article-title":"Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study","volume":"21","author":"Lonial","year":"2020","journal-title":"Lancet Oncol"},{"issue":"5","key":"2025112011214548000_bib12","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa2403407","article-title":"Belantamab mafodotin, pomalidomide, and dexamethasone in multiple myeloma","volume":"391","author":"Dimopoulos","year":"2024","journal-title":"N Engl J Med"},{"issue":"2","key":"2025112011214548000_bib13","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41591-023-02703-y","article-title":"Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1\/2 trial","volume":"30","author":"Trudel","year":"2024","journal-title":"Nat Med"},{"issue":"5","key":"2025112011214548000_bib14","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa2405090","article-title":"Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma","volume":"391","author":"Hungria","year":"2024","journal-title":"N Engl J Med"},{"issue":"10","key":"2025112011214548000_bib15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41571-024-00927-6","article-title":"BCMA-directed therapy for early relapsed and\/or refractory multiple myeloma","volume":"21","author":"van de Donk","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"issue":"24","key":"2025112011214548000_bib16","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1056\/NEJMoa2204591","article-title":"Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma","volume":"387","author":"Chari","year":"2022","journal-title":"N Engl J Med"},{"issue":"6","key":"2025112011214548000_bib17","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa2203478","article-title":"Teclistamab in relapsed or refractory multiple myeloma","volume":"387","author":"Moreau","year":"2022","journal-title":"N Engl J Med"},{"issue":"10297","key":"2025112011214548000_bib18","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0140-6736(21)00933-8","article-title":"Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b\/2 open-label study","volume":"398","author":"Berdeja","year":"2021","journal-title":"Lancet"},{"issue":"8","key":"2025112011214548000_bib19","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1056\/NEJMoa2024850","article-title":"Idecabtagene vicleucel in relapsed and refractory multiple myeloma","volume":"384","author":"Munshi","year":"2021","journal-title":"N Engl J Med"},{"issue":"9","key":"2025112011214548000_bib20","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1038\/s41591-023-02528-9","article-title":"Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results","volume":"29","author":"Lesokhin","year":"2023","journal-title":"Nat Med"},{"issue":"4","key":"2025112011214548000_bib21","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.ccell.2023.02.008","article-title":"The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients","volume":"41","author":"Friedrich","year":"2023","journal-title":"Cancer Cell"},{"issue":"6","key":"2025112011214548000_bib22","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1182\/blood.2023022823","article-title":"Correlation of immune fitness with response to teclistamab in relapsed\/refractory multiple myeloma in MajesTEC-1","volume":"144","author":"Cortes-Selva","year":"2024","journal-title":"Blood"},{"issue":"14","key":"2025112011214548000_bib23","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1158\/1078-0432.CCR-23-3333","article-title":"T-cell characteristics impact response and resistance to T-cell-redirecting bispecific antibodies in multiple myeloma","volume":"30","author":"Verkleij","year":"2024","journal-title":"Clin Cancer Res"},{"issue":"6","key":"2025112011214548000_bib24","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1158\/2643-3230.BCD-22-0018","article-title":"Changes in bone marrow tumor and immune cells correlate with durability of remissions following BCMA CAR T therapy in myeloma","volume":"3","author":"Dhodapkar","year":"2022","journal-title":"Blood Cancer Discov"},{"issue":"9","key":"2025112011214548000_bib25","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1038\/s41591-023-02496-0","article-title":"Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial","volume":"29","author":"Lin","year":"2023","journal-title":"Nat Med"},{"issue":"12","key":"2025112011214548000_bib26","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1038\/s43018-023-00657-1","article-title":"Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens","volume":"4","author":"Maura","year":"2023","journal-title":"Nat Cancer"},{"issue":"11","key":"2025112011214548000_bib27","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.ccell.2022.10.017","article-title":"Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma","volume":"40","author":"Sklavenitis-Pistofidis","year":"2022","journal-title":"Cancer Cell"},{"issue":"1","key":"2025112011214548000_bib28","doi-asserted-by":"crossref","first-page":"5335","DOI":"10.1038\/s41467-023-40966-8","article-title":"Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma","volume":"14","author":"Coffey","year":"2023","journal-title":"Nat Commun"},{"issue":"19","key":"2025112011214548000_bib29","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1182\/bloodadvances.2019000600","article-title":"T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma","volume":"3","author":"Garfall","year":"2019","journal-title":"Blood Adv"},{"issue":"5","key":"2025112011214548000_bib30","doi-asserted-by":"crossref","first-page":"e881","DOI":"10.1097\/HS9.0000000000000881","article-title":"NK cell phenotype is associated with response and resistance to daratumumab in relapsed\/refractory multiple myeloma","volume":"7","author":"Verkleij","year":"2023","journal-title":"Hemasphere"},{"issue":"9","key":"2025112011214548000_bib31","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1080\/1744666X.2022.2106217","article-title":"An immunologist's guide to immunosenescence and its treatment","volume":"18","author":"Caruso","year":"2022","journal-title":"Expert Rev Clin Immunol"},{"issue":"8","key":"2025112011214548000_bib32","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41577-021-00646-4","article-title":"Immune ageing at single-cell resolution","volume":"22","author":"Mogilenko","year":"2022","journal-title":"Nat Rev Immunol"},{"issue":"5","key":"2025112011214548000_bib33","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa1500245","article-title":"Community-acquired pneumonia requiring hospitalization among U.S. adults","volume":"373","author":"Jain","year":"2015","journal-title":"N Engl J Med"},{"issue":"7","key":"2025112011214548000_bib34","doi-asserted-by":"crossref","first-page":"e1001053","DOI":"10.1371\/journal.pmed.1001053","article-title":"Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis","volume":"8","author":"Van Kerkhove","year":"2011","journal-title":"PLoS Med"},{"key":"2025112011214548000_bib35","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1017\/S0950268818003473","article-title":"Pneumonia hospitalisation and case-fatality rates in older Australians with and without risk factors for pneumococcal disease: implications for vaccine policy","volume":"147","author":"Dirmesropian","year":"2019","journal-title":"Epidemiol Infect"},{"issue":"10","key":"2025112011214548000_bib36","doi-asserted-by":"crossref","first-page":"e13230","DOI":"10.1111\/acel.13230","article-title":"COVID-19 is an emergent disease of aging","volume":"19","author":"Santesmasses","year":"2020","journal-title":"Aging Cell"},{"issue":"4","key":"2025112011214548000_bib37","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s10096-019-03777-8","article-title":"Population-based risk factors for community-onset bloodstream infections","volume":"39","author":"Laupland","year":"2020","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"5","key":"2025112011214548000_bib38","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1093\/clinids\/2.5.801","article-title":"The effect of aging on susceptibility to infection","volume":"2","author":"Gardner","year":"1980","journal-title":"Rev Infect Dis"},{"issue":"1","key":"2025112011214548000_bib39","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41590-017-0006-x","article-title":"The twilight of immunity: emerging concepts in aging of the immune system","volume":"19","author":"Nikolich-\u017dugich","year":"2018","journal-title":"Nat Immunol"},{"issue":"6","key":"2025112011214548000_bib40","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1111\/j.1474-9726.2011.00732.x","article-title":"Vaccination-induced changes in human B-cell repertoire and pneumococcal IgM and IgA antibody at different ages","volume":"10","author":"Ademokun","year":"2011","journal-title":"Aging Cell"},{"issue":"43","key":"2025112011214548000_bib41","doi-asserted-by":"crossref","first-page":"5521","DOI":"10.1016\/j.vaccine.2008.07.071","article-title":"Pneumococcal vaccination in older adults induces antibodies with low opsonic capacity and reduced antibody potency","volume":"26","author":"Schenkein","year":"2008","journal-title":"Vaccine"},{"issue":"8","key":"2025112011214548000_bib42","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1172\/JCI57834","article-title":"Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies","volume":"121","author":"Sasaki","year":"2011","journal-title":"J Clin Invest"},{"issue":"5","key":"2025112011214548000_bib43","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.cell.2017.04.026","article-title":"Metabolic phenotypes of response to vaccination in humans","volume":"169","author":"Li","year":"2017","journal-title":"Cell"},{"issue":"8","key":"2025112011214548000_bib44","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.it.2015.06.005","article-title":"Utilizing population variation, vaccination, and systems biology to study human immunology","volume":"36","author":"Tsang","year":"2015","journal-title":"Trends Immunol"},{"issue":"52","key":"2025112011214548000_bib45","doi-asserted-by":"crossref","first-page":"8264","DOI":"10.1016\/j.vaccine.2020.11.002","article-title":"Understanding immunosenescence and its impact on vaccination of older adults","volume":"38","author":"Allen","year":"2020","journal-title":"Vaccine"},{"issue":"5","key":"2025112011214548000_bib46","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/ni.2588","article-title":"Understanding immunosenescence to improve responses to vaccines","volume":"14","author":"Goronzy","year":"2013","journal-title":"Nat Immunol"},{"issue":"10","key":"2025112011214548000_bib47","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1093\/infdis\/jiu647","article-title":"Influenza vaccine effectiveness in the United States during 2012-2013: variable protection by age and virus type","volume":"211","author":"McLean","year":"2015","journal-title":"J Infect Dis"},{"issue":"1","key":"2025112011214548000_bib48","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"issue":"10","key":"2025112011214548000_bib49","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"2025112011214548000_bib50","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41467-020-14396-9","article-title":"Sexual-dimorphism in human immune system aging","volume":"11","author":"M\u00e1rquez","year":"2020","journal-title":"Nat Commun"},{"issue":"1","key":"2025112011214548000_bib51","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2013.08.041","article-title":"Genetic variants regulating immune cell levels in health and disease","volume":"155","author":"Orr\u00f9","year":"2013","journal-title":"Cell"},{"issue":"12","key":"2025112011214548000_bib52","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1038\/s41590-021-01058-1","article-title":"Human immune diversity: from evolution to modernity","volume":"22","author":"Liston","year":"2021","journal-title":"Nat Immunol"},{"issue":"1-2","key":"2025112011214548000_bib53","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2014.12.020","article-title":"Variation in the human immune system is largely driven by non-heritable influences","volume":"160","author":"Brodin","year":"2015","journal-title":"Cell"},{"issue":"1","key":"2025112011214548000_bib54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nri.2016.125","article-title":"Human immune system variation","volume":"17","author":"Brodin","year":"2017","journal-title":"Nat Rev Immunol"},{"issue":"30","key":"2025112011214548000_bib55","doi-asserted-by":"crossref","first-page":"E6097","DOI":"10.1073\/pnas.1705065114","article-title":"Continuous immunotypes describe human immune variation and predict diverse responses","volume":"114","author":"Kaczorowski","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2025112011214548000_bib56","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/ni.3371","article-title":"The cellular composition of the human immune system is shaped by age and cohabitation","volume":"17","author":"Carr","year":"2016","journal-title":"Nat Immunol"},{"issue":"1","key":"2025112011214548000_bib57","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.smim.2015.03.003","article-title":"ImmVar project: insights and design considerations for future studies of \"healthy\" immune variation","volume":"27","author":"De Jager","year":"2015","journal-title":"Semin Immunol"},{"issue":"2","key":"2025112011214548000_bib58","doi-asserted-by":"crossref","first-page":"101628","DOI":"10.1016\/j.jgo.2023.101628","article-title":"Safety and efficacy of anti-BCMA CAR-T cell therapy in older adults with multiple myeloma: a systematic review and meta-analysis","volume":"15","author":"Akhtar","year":"2024","journal-title":"J Geriatr Oncol"},{"issue":"12","key":"2025112011214548000_bib59","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1007\/s00277-023-05451-8","article-title":"Safe and successful teclistamab treatment in very elderly multiple myeloma (MM) patients: a case report and experience from a total of three octogenarians","volume":"102","author":"Dieterle","year":"2023","journal-title":"Ann Hematol"},{"issue":"14","key":"2025112011214548000_bib60","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1200\/JCO.23.02232","article-title":"Development and validation of a prediction model of outcome after B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in relapsed\/refractory multiple myeloma","volume":"42","author":"Gagelmann","year":"2024","journal-title":"J Clin Oncol"},{"issue":"1","key":"2025112011214548000_bib61","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1182\/blood.2024025945","article-title":"Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed\/refractory multiple myeloma","volume":"145","author":"Sidana","year":"2025","journal-title":"Blood"},{"issue":"25","key":"2025112011214548000_bib62","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1200\/JCO.20.03143","article-title":"Ixazomib, daratumumab, and low-dose dexamethasone in frail patients with newly diagnosed multiple myeloma: the Hovon 143 study","volume":"39","author":"Stege","year":"2021","journal-title":"J Clin Oncol"},{"key":"2025112011214548000_bib63","doi-asserted-by":"crossref","first-page":"102167","DOI":"10.1016\/j.eclinm.2023.102167","article-title":"Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma: an open-label phase 2 trial","volume":"63","author":"Groen","year":"2023","journal-title":"EClinicalMedicine"},{"issue":"10192","key":"2025112011214548000_bib64","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","article-title":"Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study","volume":"394","author":"Moreau","year":"2019","journal-title":"Lancet"},{"issue":"4","key":"2025112011214548000_bib65","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/cyto.a.24501","article-title":"PeacoQC: peak-based selection of high quality cytometry data","volume":"101","author":"Emmaneel","year":"2022","journal-title":"Cytometry A"},{"issue":"7","key":"2025112011214548000_bib66","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/cyto.a.22625","article-title":"FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data","volume":"87","author":"Van Gassen","year":"2015","journal-title":"Cytometry A"},{"issue":"1","key":"2025112011214548000_bib67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J Stat Softw"},{"key":"2025112011214548000_bib68","doi-asserted-by":"crossref","first-page":"102229","DOI":"10.1016\/j.nicl.2020.102229","article-title":"Commentary: correction procedures in brain-age prediction","volume":"26","author":"de Lange","year":"2020","journal-title":"Neuroimage Clin"},{"issue":"5","key":"2025112011214548000_bib69","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1097\/EDE.0000000000001630","article-title":"Visualizing the (causal) effect of a continuous variable on a time-to-event outcome","volume":"34","author":"Denz","year":"2023","journal-title":"Epidemiology"},{"issue":"6","key":"2025112011214548000_bib70","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood.2024025046","article-title":"Immunotherapy: the teclistamab fitness test","volume":"144","author":"Lucca","year":"2024","journal-title":"Blood"},{"issue":"11","key":"2025112011214548000_bib71","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.4049\/jimmunol.174.11.7446","article-title":"The influence of age on T cell generation and TCR diversity","volume":"174","author":"Naylor","year":"2005","journal-title":"J Immunol"},{"issue":"2","key":"2025112011214548000_bib72","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1474-9726.2006.00204.x","article-title":"Thymic output and functionality of the IL-7\/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life","volume":"5","author":"Nasi","year":"2006","journal-title":"Aging Cell"},{"issue":"11","key":"2025112011214548000_bib73","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/j.1432-2277.2009.00927.x","article-title":"The aging of the immune system","volume":"22","author":"Weiskopf","year":"2009","journal-title":"Transpl Int"},{"issue":"2","key":"2025112011214548000_bib74","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.immuni.2012.02.006","article-title":"Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans","volume":"36","author":"den Braber","year":"2012","journal-title":"Immunity"},{"issue":"52","key":"2025112011214548000_bib75","doi-asserted-by":"crossref","first-page":"21432","DOI":"10.1073\/pnas.1209283110","article-title":"Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age","volume":"109","author":"Johnson","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2025112011214548000_bib76","doi-asserted-by":"crossref","first-page":"e426","DOI":"10.1016\/S2352-3026(20)30105-8","article-title":"Daratumumab: a game changer in myeloma therapy","volume":"7","author":"Ludwig","year":"2020","journal-title":"Lancet Haematol"},{"issue":"1","key":"2025112011214548000_bib77","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41571-021-00581-2","article-title":"Daratumumab in newly diagnosed MM - incorporating lessons learnt from CASSIOPEIA, MAIA and beyond","volume":"19","author":"Mohyuddin","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"issue":"3","key":"2025112011214548000_bib78","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41591-019-0381-y","article-title":"A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring","volume":"25","author":"Alpert","year":"2019","journal-title":"Nat Med"},{"key":"2025112011214548000_bib79","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/s43587-021-00082-y","article-title":"An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging","volume":"1","author":"Sayed","year":"2021","journal-title":"Nat Aging"},{"issue":"3","key":"2025112011214548000_bib80","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"},{"key":"2025112011214548000_bib81","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40164-018-0096-7","article-title":"Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma","volume":"7","author":"Usmani","year":"2018","journal-title":"Exp Hematol Oncol"},{"issue":"2","key":"2025112011214548000_bib82","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41375-020-0855-4","article-title":"Deep immune profiling of patients treated with lenalidomide and dexamethasone with or without daratumumab","volume":"35","author":"Casneuf","year":"2021","journal-title":"Leukemia"},{"issue":"6","key":"2025112011214548000_bib83","doi-asserted-by":"crossref","first-page":"e13028","DOI":"10.1111\/acel.13028","article-title":"Reversal of epigenetic aging and immunosenescent trends in humans","volume":"18","author":"Fahy","year":"2019","journal-title":"Aging Cell"},{"issue":"449","key":"2025112011214548000_bib84","doi-asserted-by":"crossref","first-page":"eaaq1564","DOI":"10.1126\/scitranslmed.aaq1564","article-title":"TORC1 inhibition enhances immune function and reduces infections in the elderly","volume":"10","author":"Mannick","year":"2018","journal-title":"Sci Transl Med"},{"issue":"9","key":"2025112011214548000_bib85","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s43587-023-00473-3","article-title":"Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems","volume":"3","author":"Girotra","year":"2023","journal-title":"Nat Aging"},{"issue":"7","key":"2025112011214548000_bib86","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1084\/jem.20071681","article-title":"Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets","volume":"205","author":"Sport\u00e8s","year":"2008","journal-title":"J Exp Med"},{"issue":"8006","key":"2025112011214548000_bib87","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41586-024-07238-x","article-title":"Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity","volume":"628","author":"Ross","year":"2024","journal-title":"Nature"},{"issue":"9","key":"2025112011214548000_bib88","doi-asserted-by":"crossref","first-page":"e13208","DOI":"10.1111\/acel.13208","article-title":"Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL\/6 mice","volume":"19","author":"Florian","year":"2020","journal-title":"Aging Cell"},{"issue":"2","key":"2025112011214548000_bib89","doi-asserted-by":"crossref","first-page":"e12750","DOI":"10.1111\/acel.12750","article-title":"Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood","volume":"17","author":"Duggal","year":"2018","journal-title":"Aging Cell"},{"issue":"8","key":"2025112011214548000_bib90","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.bbi.2011.07.226","article-title":"Aerobic fitness is associated with lower proportions of senescent blood T-cells in man","volume":"25","author":"Spielmann","year":"2011","journal-title":"Brain Behav Immun"},{"issue":"10","key":"2025112011214548000_bib91","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1249\/MSS.0000000000000979","article-title":"Apoptosis of T-cell subsets after acute high-intensity interval exercise","volume":"48","author":"Kr\u00fcger","year":"2016","journal-title":"Med Sci Sports Exerc"},{"issue":"6","key":"2025112011214548000_bib92","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s11357-015-9843-4","article-title":"Elderly men with moderate and intense training lifestyle present sustained higher antibody responses to influenza vaccine","volume":"37","author":"de Ara\u00fajo","year":"2015","journal-title":"Age (Dordr)"},{"issue":"12","key":"2025112011214548000_bib93","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1111\/j.1532-5415.2009.02563.x","article-title":"Cardiovascular exercise training extends influenza vaccine seroprotection in sedentary older adults: the immune function intervention trial","volume":"57","author":"Woods","year":"2009","journal-title":"J Am Geriatr Soc"},{"issue":"17-18","key":"2025112011214548000_bib94","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1016\/j.vaccine.2003.11.023","article-title":"Moderate exercise improves antibody response to influenza immunization in older adults","volume":"22","author":"Kohut","year":"2004","journal-title":"Vaccine"},{"issue":"51","key":"2025112011214548000_bib95","doi-asserted-by":"crossref","first-page":"19448","DOI":"10.1073\/pnas.0606661103","article-title":"Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates","volume":"103","author":"Messaoudi","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"S3","key":"2025112011214548000_bib96","doi-asserted-by":"crossref","first-page":"e28577c3","DOI":"10.1097\/01.HS9.0000967660.28577.c3","article-title":"S187: Immunological aging has a negative impact on clinical outcome in elderly multiple myeloma patients [abstract]","volume":"7","author":"Bruins","year":"2023","journal-title":"HemaSphere"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/146\/21\/2517\/2421312\/blood_bld-2025-028587-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/146\/21\/2517\/2421312\/blood_bld-2025-028587-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T16:22:06Z","timestamp":1763655726000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/146\/21\/2517\/546767\/A-T-cell-based-metric-of-immune-age-predicts"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":96,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11,20]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2025028587","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11,20]]},"published":{"date-parts":[[2025,11,20]]}}}