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The assessment of minimal residual disease (MRD) by next\u2010generation flow cytometry or next\u2010generation sequencing is established as a powerful predictor of long\u2010term outcomes. The use of MRD in response\u2010adapted clinical trials may provide opportunities to identify candidates for treatment escalation and de\u2010escalation. Agents with proven activity in the relapsed and refractory setting are being studied in the management of high\u2010risk newly diagnosed MM (NDMM). Here, we summarize the most recent clinical trials that have led to the current paradigms in the management of NDMM. We also discuss how novel agents could be incorporated in the newly diagnosed setting and potential clinical trial designs that could leverage MRD information with the goal of treatment optimization.<\/jats:p>","DOI":"10.1002\/ajh.26080","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T10:18:00Z","timestamp":1609755480000},"page":"367-378","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["New regimens and directions in the management of newly diagnosed multiple myeloma"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8206-8919","authenticated-orcid":false,"given":"Susan","family":"Bal","sequence":"first","affiliation":[{"name":"O'Neal Comprehensive Cancer Center University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smith","family":"Giri","sequence":"additional","affiliation":[{"name":"O'Neal Comprehensive Cancer Center University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly N.","family":"Godby","sequence":"additional","affiliation":[{"name":"O'Neal Comprehensive Cancer Center University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano J.","family":"Costa","sequence":"additional","affiliation":[{"name":"O'Neal Comprehensive Cancer Center University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.08.002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.313"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607751"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903455"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805762"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817226"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411321"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13264"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24389"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.33"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-04060-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817249"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714678"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-123426"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32956-3"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.0638"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-07-795047"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14213"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3997"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2455"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31594-X"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13780"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61424-9"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-693580"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-268862"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.099358"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2019.0049"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30578-8"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.5032"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-422683"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.2010"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.8002"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-874396"},{"key":"e_1_2_10_35_1","unstructured":"Meeting Library. 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