{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:08:53Z","timestamp":1790870933244,"version":"4.1.0"},"reference-count":26,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,22]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Circulating tumor cells (CTC) represent a high-risk biomarker in newly diagnosed multiple myeloma (NDMM); however, their prognostic value among transplant-eligible (TE) patients receiving daratumumab\/bortezomib\/lenalidomide\/dexamethasone (D-VRd) remains unknown. In this study, we analyzed CTC in the phase 3 PERSEUS\/EMN017 trial. TE-NDMM patients were randomized (1:1) to D-VRd with daratumumab\/lenalidomide maintenance (D-VRd group) or bortezomib\/lenalidomide\/dexamethasone (VRd) with lenalidomide maintenance (VRd group), both with transplant. A subset of 451 of 709 patients from PERSEUS (D-VRd, 231\/355; VRd, 220\/354) had screening blood samples collected for CTC analysis by flow cytometry. CTC were detected in 370 patients (82%; median limit of detection, 0.0004%). CTC were prognostic of progression-free survival (PFS), independent of other factors, as a continuous (hazard ratio [HR], 1.36 [95% confidence interval (CI), 1.15-1.60]; P&amp;lt; .001) and categorical variable (\u22650.175% CTC-high, optimal threshold). D-VRd improved PFS vs VRd in CTC-low patients (4-year rates: 88% vs 74%; HR, 0.42 [95% CI, 0.25-0.70]; P = .0013). Regardless of study treatment, minimal residual disease (MRD)-negativity rates were lower in CTC-high vs CTC-low patients (10\u20135: 52.2% vs 66.2%; 10\u20136: 34.8% vs 52.4%). D-VRd significantly increased MRD-negativity rates vs VRd among CTC-high (10\u20135: 69.4% vs 33.3%; 10\u20136: 47.2% vs 21.2%; both P&amp;lt; .05) and CTC-low patients (10\u20135: 74.4% vs 57.8%; 10\u20136: 65.6% vs 38.5%; both P&amp;lt; .001), with similar observations for sustained MRD-negativity. CTC levels are an independent prognostic factor in TE-NDMM treated with standard-of-care frontline quadruplet. D-VRd improved and sustained MRD-negativity rates in CTC-high and CTC-low, and improved PFS for CTC-low with a positive trend in CTC-high patients. This trial was registered at www.clinicaltrials.gov as #NCT03710603.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030113","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:50:41Z","timestamp":1759935041000},"page":"431-442","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-9696","authenticated-orcid":false,"given":"Luca","family":"Bertamini","sequence":"first","affiliation":[{"name":"1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-0590","authenticated-orcid":false,"given":"Cathelijne","family":"Fokkema","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-7785","authenticated-orcid":false,"given":"Paula","family":"Rodriguez-Otero","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Cancer Center Cl\u00ednica Universidad de Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"van Duin","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5133-1422","authenticated-orcid":false,"given":"Evangelos","family":"Terpos","sequence":"additional","affiliation":[{"name":"3Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"4Division of Hematology, AOU Citt\u00e0 della Salute e della Scienza di Torino, University of Turin, Turin, Italy"},{"name":"5Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9457-3763","authenticated-orcid":false,"given":"Vincent H. J.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"6Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-2603","authenticated-orcid":false,"given":"Niels W. C. J.","family":"van de Donk","sequence":"additional","affiliation":[{"name":"7Department of Hematology, Amsterdam University Medical Center and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0147-2291","authenticated-orcid":false,"given":"Michel","family":"Delforge","sequence":"additional","affiliation":[{"name":"8Department of Hematology, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1124-7303","authenticated-orcid":false,"given":"Christoph","family":"Driessen","sequence":"additional","affiliation":[{"name":"9Department of Medical Oncology and Hematology, Health Ostschweiz, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6955-6267","authenticated-orcid":false,"given":"Roman","family":"Hajek","sequence":"additional","affiliation":[{"name":"10Department of Hemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic"},{"name":"11Department of Hemato-oncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-0819","authenticated-orcid":false,"given":"Hermann","family":"Einsele","sequence":"additional","affiliation":[{"name":"12Department of Internal Medicine II, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2131-731X","authenticated-orcid":false,"given":"Annette","family":"Vangsted","sequence":"additional","affiliation":[{"name":"13Department of Hematology, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Vieyra","sequence":"additional","affiliation":[{"name":"14Johnson & Johnson, Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Attar","sequence":"additional","affiliation":[{"name":"14Johnson & Johnson, Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4745-6801","authenticated-orcid":false,"given":"Anna","family":"Sitthi-Amorn","sequence":"additional","affiliation":[{"name":"14Johnson & Johnson, Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Carson","sequence":"additional","affiliation":[{"name":"14Johnson & Johnson, Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-0569","authenticated-orcid":false,"given":"Fredrik","family":"Schjesvold","sequence":"additional","affiliation":[{"name":"15Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6078-5415","authenticated-orcid":false,"given":"Pawel","family":"Robak","sequence":"additional","affiliation":[{"name":"16Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1797-8657","authenticated-orcid":false,"given":"Meral","family":"Beksac","sequence":"additional","affiliation":[{"name":"17Ankara Liv Hospital, Istinye University, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Spencer","sequence":"additional","affiliation":[{"name":"18Malignant Haematology and Stem Cell Transplantation Service, Department of Clinical Haematology, Alfred Health\u2013Monash University, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-8003","authenticated-orcid":false,"given":"Annemiek","family":"Broijl","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-4273","authenticated-orcid":false,"given":"Tom","family":"Cupedo","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-8746","authenticated-orcid":false,"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"19Hematology Department, University Hospital H\u00f4tel-Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8130-5209","authenticated-orcid":false,"given":"Mario","family":"Boccadoro","sequence":"additional","affiliation":[{"name":"20European Myeloma Network, EMN Italy, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-2237","authenticated-orcid":false,"given":"Pieter","family":"Sonneveld","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"3","key":"2026012211220695300_bib1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/s41375-021-01453-5","article-title":"Mortality trends in multiple myeloma after the introduction of novel therapies in the United States","volume":"36","author":"Binder","year":"2022","journal-title":"Leukemia"},{"issue":"4","key":"2026012211220695300_bib2","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"},{"key":"2026012211220695300_bib3","unstructured":"US Food and Drug Administration\n          . FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for multiple myeloma. 2024. Accessed 3 June 2025. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-multiple."},{"key":"2026012211220695300_bib4","unstructured":"Johnson & Johnson Innovative Medicine\n          . DARZALEX\u00ae (daratumumab)-SC based quadruplet regimen approved by the European Commission for patients with newly diagnosed multiple myeloma who are transplant-eligible. 2024. 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[abstract]","volume":"144","author":"Bertamini","year":"2024","journal-title":"Blood"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2025030113\/2497647\/blood_bld-2025-030113-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2025030113\/2497647\/blood_bld-2025-030113-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:22:19Z","timestamp":1769098939000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/147\/4\/431\/547636\/Circulating-tumor-cells-predict-myeloma-outcomes"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,1,22]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2025030113","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1,22]]},"published":{"date-parts":[[2026,1,22]]}}}