{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:43:32Z","timestamp":1793105012360,"version":"4.5.0"},"reference-count":32,"publisher":"American Society of Hematology","issue":"6","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Measurable residual disease (MRD) evaluation may help to guide treatment duration in multiple myeloma (MM). Paradoxically, limited longitudinal data exist on MRD during maintenance. We investigated the prognostic value of MRD dynamics in 1280 transplant-eligible and -ineligible patients from the TOURMALINE-MM3 and -MM4 randomized placebo-controlled phase 3 studies of 2-year ixazomib maintenance. MRD status at randomization showed independent prognostic value (median progression-free survival [PFS], 38.6 vs 15.6 months in MRD\u2212 vs MRD+ patients; HR, 0.47). However, MRD dynamics during maintenance provided more detailed risk stratification. A 14-month landmark analysis showed prolonged PFS in patients converting from MRD+ to MRD\u2212 status vs those with persistent MRD+ status (76.8% vs 27.6% 2-year PFS rates). Prolonged PFS was observed in patients with sustained MRD\u2212 status vs those converting from MRD\u2212 to MRD+ status (75.0% vs 34.2% 2-year PFS rates). Similar results were observed at a 28-month landmark analysis. Ixazomib maintenance vs placebo improved PFS in patients who were MRD+ at randomization (median, 18.8 vs 11.6 months; HR, 0.65)\u00a0or at the 14-month landmark (median, 16.8 vs 10.6 months; HR, 0.65); no difference was observed in patients who were MRD\u2212. This is the largest MM population undergoing yearly MRD evaluation during maintenance reported to date. We demonstrate the limited prognostic value of a single\u2013time point MRD evaluation, because MRD dynamics over time substantially impact PFS risk. These findings support MRD\u2212 status as a\u00a0relevant end point during maintenance and confirm the increased progression risk in patients converting to MRD+\u00a0from MRD\u2212 status. These trials were registered at www.clinicaltrials.gov as #NCT02181413 and #NCT02312258.<\/jats:p>","DOI":"10.1182\/blood.2022016782","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T21:09:29Z","timestamp":1663794569000},"page":"579-591","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":62,"title":["MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-3815","authenticated-orcid":false,"given":"Bruno","family":"Paiva","sequence":"first","affiliation":[{"name":"1Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), CIBERONC (CB16\/12\/00369), Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Manrique","sequence":"additional","affiliation":[{"name":"1Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), CIBERONC (CB16\/12\/00369), Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"2Hematology and Medical Oncology, Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-412X","authenticated-orcid":false,"given":"Francesca","family":"Gay","sequence":"additional","affiliation":[{"name":"3Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria City of Health and Science of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Ki","family":"Min","sequence":"additional","affiliation":[{"name":"4Department of Internal Medicine, Seoul St Mary\u2019s Hospital, Catholic University of Korea, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[{"name":"5Department of Hematology, Amsterdam University Medical Center, VU University Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"\u0160pi\u010dka","sequence":"additional","affiliation":[{"name":"6Department of Hematology, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Teipel","sequence":"additional","affiliation":[{"name":"7Medizinische Klinik und Poliklinik I, Universit\u00e4tsklinikum TU Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Mar\u00eda-Victoria","family":"Mateos","sequence":"additional","affiliation":[{"name":"8University Hospital of Salamanca, CIC, IBMCC, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Giuliani","sequence":"additional","affiliation":[{"name":"9Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, and Ematologia e CTMO, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cavo","sequence":"additional","affiliation":[{"name":"10IRCCS 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"}]},{"given":"Christine Rojas","family":"Hopkins","sequence":"additional","affiliation":[{"name":"11Cl\u00ednica Bupa Re\u00f1aca, Universidad de Valpara\u00edso, Vi\u00f1a del Mar, Valpara\u00edso, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-0207","authenticated-orcid":false,"given":"Weijun","family":"Fu","sequence":"additional","affiliation":[{"name":"12Department of Hematology, Shanghai Changzheng Hospital, Shanghai, China"},{"name":"13Department of Hematology, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaveri","family":"Suryanarayan","sequence":"additional","affiliation":[{"name":"14Takeda Development Center Americas, Lexington, 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