{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:41:08Z","timestamp":1777398068855,"version":"3.51.4"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In multiple myeloma (MM), minimal residual disease (MRD) is an established endpoint for accelerated drug approval but is limited by a need for serial invasive bone marrow (BM) biopsies, which may under\u2010sample spatial heterogeneity and result in false negativity. Furthermore, longitudinal (i.e., sustained) MRD negativity is emerging as a powerful tool for clinical decision\u2010making. To these ends, reliable systemic MRD assessment is a growing need. Next\u2010generation sequencing approaches for plasma cell\u2010free (cf) DNA generally fail to achieve adequate detection limits in low tumor fraction (TF) settings (i.e., MRD), but tumor\u2010informed approaches leveraging whole\u2010genome sequencing (WGS) have thus far achieved the lowest limits of detection (LODs). We therefore performed a longitudinal analysis of MRD assessed by serial WGS of plasma cfDNA as compared to clinical standard flow\u2010cytometric BM MRD in high\u2010risk smoldering MM. 25 baseline tumor WGS served to inform detection of disease in 87 sequential plasma samples. The median LOD across patients was 1.2\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    (range 9.0\u2009\u00d7\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    \u2013 2.1 \u00d7 10\n                    <jats:sup>\u22124<\/jats:sup>\n                    ). TF was prognostic, and tumors with high\u2010risk genomics had higher baseline TF (P\u2009=\u20090.002) and eventual disease progression (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097, P\u2009&lt;\u20090.001). Furthermore, dynamic changes in serially tracked TF portended outcome. In comparison to BM flow, cfDNA WGS was concordant in 33\/45 (73.3%) MRD samples with consistent capture of BM\u2010positive cases, but added resolution to apparent false\u2010negative BM samples. Overall, despite the deeper LOD of localized BM flow, cfDNA WGS can detect MRD when BM flow did not, adding dynamic and systemic\/spatial resolution to standard hyper\u2010local MRD assessment.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70367","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:15:20Z","timestamp":1776338120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole\u2010genome sequencing of cell\u2010free DNA for assessment of minimal residual disease in high\u2010risk smoldering multiple myeloma"],"prefix":"10.1002","volume":"10","author":[{"given":"Chrissy","family":"Baker","sequence":"first","affiliation":[{"name":"Myeloma Institute Sylvester Comprehensive Cancer Center, University of Miami Miami Florida 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