{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T10:55:15Z","timestamp":1780397715008,"version":"3.54.1"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"cris against the cancer","award":["18001"],"award-info":[{"award-number":["18001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The assessment of measurable residual disease (MRD) in bone marrow has proven of prognostic relevance in patients with multiple myeloma (MM). Nevertheless, and unlike other hematologic malignancies, the use of MRD results to make clinical decisions in MM has been underexplored to date. In this retrospective study, we present the results from a multinational and multicenter series of 400 patients with MRD monitoring during front-line therapy with the aim of exploring how clinical decisions made based on those MRD results affected outcomes. As expected, achievement of MRD negativity at any point was associated with improved PFS versus persistent MRD positivity (median PFS 104 vs. 45\u00a0months, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). In addition, however, 67 out of 400 patients underwent a clinical decision (treatment discontinuation, intensification or initiation of a new therapy) based on MRD results. Those patients in whom a treatment change was made showed a prolonged PFS in comparison with those 333 patients in which MRD results were not acted upon (respectively, mPFS 104 vs. 62\u00a0months, <jats:italic>p<\/jats:italic>\u2009=\u20090.005). In patients who achieved MRD negativity during maintenance (<jats:italic>n<\/jats:italic>\u2009=\u2009186) on at least one occasion, stopping therapy in 24 patients vs. continuing in 162 did not alter PFS (mPFS 120\u00a0months vs. 82\u00a0months, <jats:italic>p<\/jats:italic>\u2009=\u20090.1). Most importantly, however, in patients with a positive MRD during maintenance (<jats:italic>n<\/jats:italic>\u2009=\u2009214), a clinical decision (either intensification or change of therapy) (<jats:italic>n<\/jats:italic>\u2009=\u200943) resulted in better PFS compared to patients in whom no adjustment was made (<jats:italic>n<\/jats:italic>\u2009=\u2009171) (mPFS NA vs. 39\u00a0months, <jats:italic>p<\/jats:italic>\u2009=\u20090.02). Interestingly, there were no significant differences when MRD was assessed by flow cytometry or by next-generation sequencing. Herein, we find that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients. This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.<\/jats:p>","DOI":"10.1186\/s13045-021-01135-w","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T11:03:08Z","timestamp":1629198188000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Making clinical decisions based on measurable residual disease improves the outcome in multiple myeloma"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-0063","authenticated-orcid":false,"given":"Joaquin","family":"Martinez-Lopez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy W.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Rios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanira","family":"Ruiz-Heredia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Maria","family":"Sanchez-Pina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Bahri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Zamanillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Poza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Buenache","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Encinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Juarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Miras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Collado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Barrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Cedena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"issue":"23","key":"1135_CR1","doi-asserted-by":"publisher","first-page":"5988","DOI":"10.1182\/bloodadvances.2020002827","volume":"4","author":"NC Munshi","year":"2020","unstructured":"Munshi NC, Avet-Loiseau H, Anderson KC, et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv. 2020;4(23):5988\u201399. https:\/\/doi.org\/10.1182\/bloodadvances.2020002827.","journal-title":"Blood Adv"},{"issue":"25","key":"1135_CR2","doi-asserted-by":"publisher","first-page":"2900","DOI":"10.1200\/JCO.2016.69.2517","volume":"35","author":"J-J Lahuerta","year":"2017","unstructured":"Lahuerta J-J, Paiva B, Vidriales M-B, et al. Depth of response in multiple myeloma: a pooled analysis of three PETHEMA\/GEM clinical trials. J Clin Oncol. 2017;35(25):2900\u201310. https:\/\/doi.org\/10.1200\/JCO.2016.69.2517.","journal-title":"J Clin Oncol"},{"issue":"20","key":"1135_CR3","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.1182\/blood-2014-01-550020","volume":"123","author":"J Martinez-Lopez","year":"2014","unstructured":"Martinez-Lopez J, Lahuerta JJ, Pepin F, et al. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014;123(20):3073\u20139. https:\/\/doi.org\/10.1182\/blood-2014-01-550020.","journal-title":"Blood"},{"issue":"8","key":"1135_CR4","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1200\/JCO.19.01231","volume":"38","author":"B Paiva","year":"2020","unstructured":"Paiva B, Puig N, Cedena M-T, et al. Measurable residual disease by next-generation flow cytometry in multiple myeloma. J Clin Oncol. 2020;38(8):784\u201392. https:\/\/doi.org\/10.1200\/JCO.19.01231.","journal-title":"J Clin Oncol"},{"issue":"8","key":"1135_CR5","doi-asserted-by":"publisher","first-page":"e328","DOI":"10.1016\/S1470-2045(16)30206-6","volume":"17","author":"S Kumar","year":"2016","unstructured":"Kumar S, Paiva B, Anderson KC, et al. International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328\u201346. https:\/\/doi.org\/10.1016\/S1470-2045(16)30206-6.","journal-title":"Lancet Oncol"},{"issue":"1","key":"1135_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1053\/j.seminhematol.2018.03.003","volume":"55","author":"O Landgren","year":"2018","unstructured":"Landgren O. MRD Testing in multiple myeloma: from a surrogate marker of clinical outcomes to an every-day clinical tool. Semin Hematol. 2018;55(1):1\u20133. https:\/\/doi.org\/10.1053\/j.seminhematol.2018.03.003.","journal-title":"Semin Hematol"},{"issue":"14","key":"1135_CR7","doi-asserted-by":"publisher","first-page":"3295","DOI":"10.1182\/bloodadvances.2020002037","volume":"4","author":"J Martinez-Lopez","year":"2020","unstructured":"Martinez-Lopez J, Wong SW, Shah N, et al. Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma. Blood Adv. 2020;4(14):3295\u2013301. https:\/\/doi.org\/10.1182\/bloodadvances.2020002037.","journal-title":"Blood Adv"},{"issue":"1","key":"1135_CR8","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S1470-2045(18)30687-9","volume":"20","author":"GH Jackson","year":"2019","unstructured":"Jackson GH, Davies FE, Pawlyn C, et al. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20(1):57\u201373. https:\/\/doi.org\/10.1016\/S1470-2045(18)30687-9.","journal-title":"Lancet Oncol"},{"key":"1135_CR9","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26150","author":"N Korde","year":"2021","unstructured":"Korde N, Mastey D, Tavitian E, et al. Tailored treatment to MRD response: a phase I\/II study for newly diagnosed multiple myeloma patients using high dose twice-weekly carfilzomib (45 and 56 mg\/m2) in combination with lenalidomide and dexamethasone. Am J Hematol. 2021. https:\/\/doi.org\/10.1002\/ajh.26150.","journal-title":"Am J Hematol"},{"issue":"Supplement_1","key":"1135_CR10","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1182\/blood-2019-123170","volume":"134","author":"LJ Costa","year":"2019","unstructured":"Costa LJ, Chhabra S, Godby KN, et al. Blood. 2019;134(Supplement_1):860\u2013860. https:\/\/doi.org\/10.1182\/blood-2019-123170.","journal-title":"Blood"},{"issue":"Supplement 1","key":"1135_CR11","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1182\/blood.V130.Suppl_1.435.435","volume":"130","author":"H Avet-Loiseau","year":"2017","unstructured":"Avet-Loiseau H, Lauwers-Cances V, Corre J, Moreau P, Attal M, Munshi N. 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J Hematol Oncol. 2020. https:\/\/doi.org\/10.1186\/s13045-020-00911-4.","journal-title":"J Hematol Oncol"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-021-01135-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13045-021-01135-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-021-01135-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T11:12:59Z","timestamp":1629198779000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-021-01135-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,17]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1135"],"URL":"https:\/\/doi.org\/10.1186\/s13045-021-01135-w","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,17]]},"assertion":[{"value":"29 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Institutional Review Board (IRB) of University Hospital 12 de Octubre (n# 20\/326) and UCSF. Written informed consent was waived in light of the retrospective nature and need to collect and report data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"JML. Speaking bureau of Adaptive, owner of shares of Altum sequencing and Hosea. JW. Consultant for Adaptive. SB. Owner of shares of Altum sequencing. RA, RR, NS, YRH, JMSP, RS, NB, IZ, MP, NB, CE, LJ, FM, LC, TM declare no competing financial interests, this must be explicitly stated and will be included in all versions of the article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"126"}}