{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:53:33Z","timestamp":1790409213375,"version":"4.1.0"},"reference-count":28,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Quadruplet therapy with Isa-VRd (isatuximab, Velcade [bortezomib], Revlimid [lenalidomide], and dexamethasone) followed by Isa-Rd in the randomized phase 3 IMROZ study provided a significant progression-free survival benefit to transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). In the primary analysis, more Isa-VRd\/Isa-Rd\u2013treated patients achieved minimal residual disease (MRD) negativity and MRD-negative complete response (CR) at any time point than patients receiving VRd followed by Rd. Here, we report landmark analysis results of MRD negativity over time and its impact on clinical outcomes in IMROZ. Treatment with Isa-VRd\/Isa-Rd led to deeper responses, with higher rates of MRD negativity and MRD-negative CR at the end of induction and during maintenance vs VRd\/Rd, up to 60 months of follow-up. Benefit with Isa-VRd\/Isa-Rd was observed across key patient subgroups, including older (&amp;gt;70 years) and frail patients. Time to progression (TTP) was significantly prolonged with Isa-VRd\/Isa-Rd vs VRd\/Rd in patients who converted from MRD negative to MRD positive at any time point. In a landmark analysis of the time of conversion to MRD positivity, TTP in patients who converted from MRD negative at the end of induction to MRD positive also favored Isa-VRd\/Isa-Rd. Evaluating MRD status of patients at &amp;gt;1 time point may therefore be useful to support decisions on treatment selection and treatment continuation\/discontinuation. Our findings on the degree of MRD negativity and MRD-negative CR benefit achieved during induction and maintenance by patients receiving Isa-VRd\/Isa-Rd vs VRd\/Rd extend the IMROZ primary analyses and further support Isa-VRd as standard of care for frontline treatment of transplant-ineligible patients with NDMM. This trial was registered at www.clinicaltrials.gov as #NCT03319667.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030120","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:54:30Z","timestamp":1772218470000},"page":"2760-2769","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma: dynamics of MRD negativity in the IMROZ study"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-4129","authenticated-orcid":false,"given":"Robert Z.","family":"Orlowski","sequence":"first","affiliation":[{"name":"1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"2Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"3Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece"},{"name":"4Department of Medicine, Korea University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-4170","authenticated-orcid":false,"given":"Xavier","family":"Leleu","sequence":"additional","affiliation":[{"name":"5Service d'H\u00e9matologie et Th\u00e9rapie Cellulaire, Centre Hospitalier Universitaire and Centre d'Investigation Clinique, INSERM 1402, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-8460","authenticated-orcid":false,"given":"Thierry","family":"Facon","sequence":"additional","affiliation":[{"name":"6Department of Hematology, University Hospital and INSERM Unit\u00e9 Mixte de Recherche S1277, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-3292","authenticated-orcid":false,"given":"Tadao","family":"Ishida","sequence":"additional","affiliation":[{"name":"7Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6955-6267","authenticated-orcid":false,"given":"Roman","family":"H\u00e1jek","sequence":"additional","affiliation":[{"name":"8Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"\u0160pi\u010dka","sequence":"additional","affiliation":[{"name":"9Charles University and General Faculty Hospital in Prague, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-1112","authenticated-orcid":false,"given":"Joanna","family":"Romejko-Jarosinska","sequence":"additional","affiliation":[{"name":"10Department of Lymphoid Malignancies, Marie Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2692-8961","authenticated-orcid":false,"given":"Vladimir","family":"Vorobyev","sequence":"additional","affiliation":[{"name":"11SP Botkin Moscow City Clinical Hospital, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Besemer","sequence":"additional","affiliation":[{"name":"12Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9310-1278","authenticated-orcid":false,"given":"Sevgi Kalayo\u011flu","family":"Be\u015f\u0131\u015f\u0131k","sequence":"additional","affiliation":[{"name":"13Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6078-5415","authenticated-orcid":false,"given":"Pawel","family":"Robak","sequence":"additional","affiliation":[{"name":"14Department of General Hematology, Copernicus Memorial Hospital, Comprehensive Cancer Center and Traumatology, \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-9253","authenticated-orcid":false,"given":"Tomas","family":"Jelinek","sequence":"additional","affiliation":[{"name":"8Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-0035","authenticated-orcid":false,"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"15Internal Medicine V, Hematology, Oncology and Rheumatology, German-speaking Myeloma Multicenter Group\u2013Study Group, Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Martin","sequence":"additional","affiliation":[{"name":"16Department of Hematology, University of California at San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7264-808X","authenticated-orcid":false,"given":"Mohamad","family":"Mohty","sequence":"additional","affiliation":[{"name":"17Department of Hematology, H\u00f4pital Saint-Antoine, Sorbonne University and INSERM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-6994","authenticated-orcid":false,"given":"Sandrine","family":"Mac\u00e9","sequence":"additional","affiliation":[{"name":"18R&D, Sanofi, Vitry-sur-Seine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ercem","family":"Kodas","sequence":"additional","affiliation":[{"name":"18R&D, Sanofi, Vitry-sur-Seine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Tekle","sequence":"additional","affiliation":[{"name":"19Sanofi, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea 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