{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T04:32:26Z","timestamp":1793939546194,"version":"4.8.0"},"reference-count":53,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The clinical significance of 1 or 2 measurable residual disease (MRD) assessments is established in multiple myeloma (MM). However, how to stratify patients according to \u22653 MRD assessments remains unknown. The traits of MRD resistance and whether treatment of persistent MRD vs relapse could improve outcomes remains unknown. MRD dynamics were computed using next-generation flow cytometry and CONNECTOR in 539 patients with newly diagnosed MM with \u22653 assessments in the GEM2012MENOS65\/GEM2014MAIN and GEM2017FIT trials. Molecular and immune profiling were performed in matched diagnostic and MRD samples. The survival impact of treating persistent MRD vs relapse was investigated with anti\u2013B-cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cells in MIc\u03b31hCRBN mice. Computed MRD dynamics based on 3610 MRD assessments identified 5 subgroups with different survival. Patients with late-sustained MRD response had excellent outcomes, similar to those with early sustained MRD response. Patients with volatile results and those with primarily and resurgent MRD resistance had dismal survival. MRD dynamics outperformed transplant eligibility and the Revised International Staging System. These results were validated in 249 patients with MM treated in routine practice. Multiomics characterization of MRD dynamics in patients and mouse models of MRD resistance revealed genomic evolution, transcriptional adaptation, and a proinflammatory tumor-immune microenvironment. Increasing clonality and exhaustion of endogenous T cells throughout disease progression urged investigating whether MRD interception with anti-BCMA CAR T cells could improve outcomes. Infusion at MRD resistance prolonged mouse survival compared with identical treatment at relapse. In summary, MRD dynamics is the strongest predictor of progression and may help tailoring treatment to prevent additional tumor and immune alterations before relapse.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2026033878","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:14:14Z","timestamp":1784945654000},"page":"2368-2383","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["MRD dynamics predicts progression and reveals a vulnerable state for immunotherapy interception in multiple myeloma"],"prefix":"10.1182","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3074-9229","authenticated-orcid":false,"given":"Carmen","family":"Gonzalez","sequence":"first","affiliation":[{"name":"1Cancer Center Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, CIBER-ONC number CB16\/12\/00369, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Guerrero","sequence":"additional","affiliation":[{"name":"1Cancer Center Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, CIBER-ONC number CB16\/12\/00369, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Larrayoz","sequence":"additional","affiliation":[{"name":"2Cancer Center Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, CIBER-ONC number CB16\/12\/00489, Pamplona, 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