{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T21:46:19Z","timestamp":1775598379044,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The treatment landscape for older patients with multiple myeloma (MM) has rapidly evolved with the introduction of CD38\u2010targeting antibodies. Yet, outcomes remain highly variable and are only partially explained by frailty status. To address this, we investigated the impact of the immune system on survival outcomes of 89 newly diagnosed MM patients in the HOVON\u2010143 trial, where frail or intermediate\u2010fit patients received daratumumab\u2013ixazomib\u2013dexamethasone. Comprehensive immunophenotyping of lymphoid and myeloid subsets as relative or absolute counts in peripheral blood (PB) and bone marrow revealed comparable immune composition between frail and intermediate\u2010fit patients at diagnosis, except for reduced naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells and increased effector memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells and CD56\n                    <jats:sup>bright<\/jats:sup>\n                    NK\u2010cells in frail patients. Among 36 T\u2010cell and NK\u2010cell subsets analyzed, 9 subsets\u2014measured as absolute counts in PB\u2014showed strong association with progression\u2010free survival (PFS) and 5 with overall survival (OS). Four subsets were linked to both PFS and OS: higher absolute counts of naive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells, CD38\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells, and CD56\n                    <jats:sup>dim<\/jats:sup>\n                    CD57\n                    <jats:sup>+<\/jats:sup>\n                    NK\u2010cells were associated with longer survival, whereas elevated EM CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell counts were linked to shorter survival. Using the most predictive immune parameters, we subsequently developed two immune risk scores\u2014one for PFS and one for OS\u2014which remained strongly associated with survival after adjusting for frailty status, disease stage, and cytogenetic risk. Our findings underscore the importance of a composite analysis of the immune system and demonstrate the association of baseline immune parameters with survival outcomes of first\u2010line therapy in non\u2010fit MM patients.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70210","type":"journal-article","created":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T19:54:31Z","timestamp":1759694071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immune signatures in older patients with newly diagnosed multiple myeloma are associated with survival outcomes of first\u2010line therapy irrespective of frailty levels"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-9257","authenticated-orcid":false,"given":"Wassilis S. C.","family":"Bruins","sequence":"first","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-9550","authenticated-orcid":false,"given":"Febe","family":"Smits","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"},{"name":"Department of Hematology Haga Hospital The Hague The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolien","family":"Duetz","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazem","family":"Nasserinejad","sequence":"additional","affiliation":[{"name":"Department of Hematology HOVON Data Center, Erasmus MC Cancer Institute Rotterdam The Netherlands"},{"name":"Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7750-4359","authenticated-orcid":false,"given":"Kazimierz","family":"Groen","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0191-4343","authenticated-orcid":false,"given":"Charlotte L. B. M.","family":"Korst","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-1762","authenticated-orcid":false,"given":"A. Vera","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Rentenaar","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Hageman","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meliha","family":"Cosovic","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Eken","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inoka","family":"Twickler","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola M.","family":"Homan\u2010Weert","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christie P. M.","family":"Verkleij","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine","family":"Frerichs","sequence":"additional","affiliation":[{"name":"Hematology Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Cancer Biology and Immunology Cancer Center Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark\u2010David","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Albert Schweitzer Hospital Dordrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"van der Spek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Rijnstate Hospital Arnhem The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inger S.","family":"Nijhof","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Hematology St Antonius Hospital Nieuwegein The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roel","family":"van Kampen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Zuyderland Hospital Sittard The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-2603","authenticated-orcid":false,"given":"Niels W. 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