{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:55:01Z","timestamp":1791881701792,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Measurable residual disease assessment in bone marrow (BM\u2010MRD) is a crucial prognostic factor in multiple myeloma (MM), but its clinical use has some caveats, such as invasiveness, poor spatial representativity, and serial sampling. Novel minimally invasive approaches for monitoring peripheral residual disease (PRD) could facilitate its clinical use. We aimed to investigate a sensitive method for detecting PRD in patients with MM. This study included 84 patients enrolled in PETHEMA\/GEM clinical trials, and a total of 292 longitudinal samples were analyzed. BM\u2010MRD in these patients was assessed using EuroFlow\u2010based next\u2010generation flow cytometry (NGF) and PRD was simultaneously examined in cell\u2010free DNA (cfDNA) using AltumTrackSeq\u00ae, a highly sensitive next\u2010generation sequencing (NGS) method based on patient\u2010specific multiplexed amplicon mini\u2010panels that target somatic mutations identified at diagnosis. Our findings revealed that automated isolation methods enabled standardization and yielded cfDNA levels comparable to manual protocols. A high median cfDNA concentration of 393.2\u2009ng was obtained, with a range from 17.3 to 6300\u2009ng. Furthermore, we demonstrated that compared with traditional BM\u2010MRD by NGF, our ctDNA\u2010NGS approach showed a higher positive predictive value (PPV, 88.9% vs. 34.5%) and specificity (Sp, 98.4% vs. 70.3%) for predicting relapse during the follow\u2010up period. Detectable ctDNA was associated with a high risk of progression and\/or death (HR, 11.5; 95% CI, 2.66\u201349.4), and this was confirmed in the multivariate analysis. In conclusion, this assay offers a method for detecting imminent relapse risk in the peripheral blood of MM patients.<\/jats:p>","DOI":"10.1002\/hem3.70405","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:27:23Z","timestamp":1781803643000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Minimally invasive characterization of peripheral blood measurable residual disease in multiple myeloma using high\u2010sensitivity detection of ctDNA by next\u2010generation sequencing"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9145-3462","authenticated-orcid":false,"given":"Natalia","family":"Buenache","sequence":"first","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Lasa","sequence":"additional","affiliation":[{"name":"Cancer Center Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA) Universidad de Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Arroyo","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3074-9229","authenticated-orcid":false,"given":"Carmen","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Cancer Center Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA) Universidad de Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3927-9163","authenticated-orcid":false,"given":"Larissa","family":"Haertle","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"},{"name":"Department of Medicine III, Technical University of Munich, School of Medicine and Health TUM University Hospital Munich Germany"},{"name":"TranslaTUM, Center for Translational Cancer Research Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanira","family":"Ruiz\u2010Heredia","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Ayala","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3774-118X","authenticated-orcid":false,"given":"Rafael","family":"Alonso","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Mart\u00edn\u2010Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Altum Sequencing Co. Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Rosa\u2010Rosa","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Salamanca, Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca, Salamanca (IBSAL) Universidad de Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Calasanz","sequence":"additional","affiliation":[{"name":"Cancer Center Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA) Universidad de Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-7785","authenticated-orcid":false,"given":"Paula","family":"Rodr\u00edguez\u2010Otero","sequence":"additional","affiliation":[{"name":"Cancer Center Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA) Universidad de Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rosi\u00f1ol","sequence":"additional","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology, IDIBAPS Hospital Cl\u00ednic de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4451-1318","authenticated-orcid":false,"given":"Felipe","family":"De Arriba","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda. Hospital General Universitario Morales Meseguer. Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB\u2010Pascual Parrilla) Universidad de Murcia Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique M.","family":"Ocio","sequence":"additional","affiliation":[{"name":"Hospital Universitario Marqu\u00e9s de Valdecilla (IDIVAL), Universidad de Cantabria Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Oriol","sequence":"additional","affiliation":[{"name":"Institut Catal\u00e0 d'Oncologia i Institut Josep Carreras Hospital Germans Trias i Pujol, Badalona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Institut d'Oncologia Dr. Josep Trueta Girona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sureda","sequence":"additional","affiliation":[{"name":"Institut Catal\u00e0 D'Oncologia, Hospital Duran i Reynals, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL) Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-4839","authenticated-orcid":false,"given":"Sunil","family":"Lakhwani","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Canarias Santa Cruz de Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"Clavero","sequence":"additional","affiliation":[{"name":"Hospital Virgen de las Nieves Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Complejo Hospitalario Universitario de Albacete Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Galdakao Vizcaya Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Salamanca, Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca, Salamanca (IBSAL) Universidad de Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda\u2010Victoria","family":"Mateos","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Salamanca, Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca, Salamanca (IBSAL) Universidad de Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Lahuerta","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda T.","family":"Cedena","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Blad\u00e9","sequence":"additional","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology, IDIBAPS Hospital Cl\u00ednic de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"San Miguel","sequence":"additional","affiliation":[{"name":"Cancer Center Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA) Universidad de Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-3861","authenticated-orcid":false,"given":"Noemi","family":"Puig","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Salamanca, Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca, Salamanca (IBSAL) Universidad de Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-3815","authenticated-orcid":false,"given":"Bruno","family":"Paiva","sequence":"additional","affiliation":[{"name":"Cancer Center Clinica Universidad de Navarra, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA) Universidad de Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Mart\u00ednez\u2010L\u00f3pez","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Clinical Research Unit, Hospital Universitario 12 de Octubre Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-550020"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.3160"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01231"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25507"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00635"},{"issue":"3","key":"e_1_2_11_7_1","first-page":"646","article-title":"Free DNA in the serum of cancer patients and the effect of therapy","volume":"37","author":"Leon SA","year":"1977","journal-title":"Cancer Res"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000226740"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3247"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000499337"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00837-3"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-00981-w"},{"key":"e_1_2_11_13_1","article-title":"Somatic mutation phasing and haplotype extension using linked\u2010reads in multiple myeloma","author":"Foltz SM","year":"2024","journal-title":"bioRxiv"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01803-x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188818"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003732"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14205169"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI154941"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.194712"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-57570-5"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.29"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.69.2517"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-189095"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1691"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2018.298323"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr.2016.12.03"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/1010428320916314"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz8084"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.28581"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0187-3"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-02017-9"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1172108"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15143687"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04001-5"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.184358"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15086"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023022540"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01365"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-06-858613"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005822"}],"container-title":["HemaSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70405","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hem3.70405","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:34:32Z","timestamp":1791880472000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hem3.70405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/hem3.70405"],"URL":"https:\/\/doi.org\/10.1002\/hem3.70405","archive":["Portico"],"relation":{},"ISSN":["2572-9241","2572-9241"],"issn-type":[{"value":"2572-9241","type":"print"},{"value":"2572-9241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70405"}}