{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:10:12Z","timestamp":1790824212366,"version":"4.1.0"},"reference-count":27,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We explored minimal residual disease (MRD) in relapsed\/refractory multiple myeloma (RRMM) and transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) using data from 4 phase 3 studies (POLLUX, CASTOR, ALCYONE, and MAIA). Each study previously demonstrated that daratumumab-based therapies improved MRD negativity rates and reduced the risk of disease progression or death by approximately half vs standards of care. We conducted a large-scale pooled analysis for associations between patients achieving complete response or better (\u2265CR) with MRD-negative status and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10\u22125 sensitivity threshold). Patient-level data were pooled from all 4 studies and for patients with TIE NDMM and patients with RRMM who received \u22642 prior lines of therapy (\u22642 PL). PFS was evaluated by response and MRD status. Median follow-up (months) was 54.8 for POLLUX, 50.2 for CASTOR, 40.1 for ALCYONE, and 36.4 for MAIA. Patients who achieved \u2265CR and MRD negativity had improved PFS vs those who failed to reach CR or were MRD positive (TIE NDMM and RRMM hazard ratio [HR] 0.20, P &amp;lt; .0001; TIE NDMM and RRMM \u22642 PL HR 0.20, P &amp;lt; .0001). This benefit occurred irrespective of therapy or disease setting. A time-varying Cox proportional hazard model confirmed that \u2265CR with MRD negativity was associated with improved PFS. Daratumumab-based treatment was associated with more patients reaching \u2265CR and MRD negativity. These findings represent the first large-scale analysis with robust methodology to support \u2265CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM. These trials were registered at www.clinicaltrials.gov as #NCT02076009, #NCT02136134, #NCT02195479, and #NCT02252172.<\/jats:p>","DOI":"10.1182\/blood.2021011101","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T18:00:14Z","timestamp":1626890414000},"page":"835-844","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":101,"title":["Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA"],"prefix":"10.1182","volume":"139","author":[{"given":"Michele","family":"Cavo","sequence":"first","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Universit\u00e0 di Bologna, Bologna, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9183-4857","authenticated-orcid":false,"given":"Jesus","family":"San-Miguel","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n Medica Aplicada (CIMA), IDISNA, CIBER-ONC, Pamplona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad Z.","family":"Usmani","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute\/Atrium Health, Charlotte, NC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Weisel","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens, Athens, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Avet-Loiseau","sequence":"additional","affiliation":[{"name":"Unite de Genomique du Myelome, IUC-Oncopole, Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-3815","authenticated-orcid":false,"given":"Bruno","family":"Paiva","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Centro de Investigaci\u00f3n Medica Aplicada (CIMA), IDISNA, CIBER-ONC, Pamplona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nizar J.","family":"Bahlis","sequence":"additional","affiliation":[{"name":"Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Plesner","sequence":"additional","affiliation":[{"name":"Vejle Hospital and University of Southern Denmark, Vejle, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4327-1957","authenticated-orcid":false,"given":"Vania","family":"Hungria","sequence":"additional","affiliation":[{"name":"Clinica Medica S\u00e3o Germano, S\u00e3o Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"Hematology, University Hospital H\u00f4tel-Dieu, CHU Nantes, Nantes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Maria-Victoria","family":"Mateos","sequence":"additional","affiliation":[{"name":"University Hospital of Salamanca\/IBSAL\/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-8689","authenticated-orcid":false,"given":"Aurore","family":"Perrot","sequence":"additional","affiliation":[{"name":"Hematology Department, University Cancer Institute IUCT, Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-960X","authenticated-orcid":false,"given":"Shinsuke","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku Nagoya, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Facon","sequence":"additional","affiliation":[{"name":"University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-9284","authenticated-orcid":false,"given":"Shaji","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Hematology, Mayo Clinic Rochester, Rochester, MN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels W. 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