{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:15:35Z","timestamp":1792732535937,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Induction and consolidation with a quadruplet therapy of a CD38-targeting monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug and dexamethasone are a standard-of-care treatment in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) with the optimal drugs to be used still under debate. The ongoing, phase 3 EMN24 IsKia trial randomized 302 TE patients with NDMM aged \u226470\u2009years 1:1 to isatuximab\u2013carfilzomib\u2013lenalidomide\u2013dexamethasone (Isa-KRd) versus KRd pretransplant induction and post-transplant consolidation. The primary endpoint was the rate of measurable residual disease (MRD) negativity (sensitivity of 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    or better) by next-generation sequencing (NGS) after consolidation. Key secondary endpoints were the rates of NGS-MRD negativity after induction and progression-free survival (PFS). MRD negativity rates at higher sensitivity (10\n                    <jats:sup>\u22126<\/jats:sup>\n                    or better) were exploratory. Post-consolidation MRD negativity was significantly higher with Isa-KRd versus KRd at the 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    (77% versus 67%; odds ratio (OR) 1.67,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.049) and 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    (68% versus 48%; OR 2.36,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0004) sensitivities. Deep MRD responses were rapid (post-induction Isa-KRd versus KRd: 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    46% versus 27%, OR 2.32,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0007; 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    28% versus 14%, OR 2.44,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0029) and durable (1-year sustained 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    MRD negativity 52% versus 38%, OR 1.82,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.012). At current follow-up, PFS data were immature. Grade 3\u20134 non-hematologic adverse events (AEs), treatment discontinuations and deaths due to AEs were similar in the two arms. Isa-KRd significantly improved NGS-MRD negativity in TE patients with NDMM, with a manageable safety profile. ClinicalTrials.gov registration:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04483739\" ext-link-type=\"uri\">NCT04483739<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04282-0","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T09:02:39Z","timestamp":1775466159000},"page":"1773-1782","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-412X","authenticated-orcid":false,"given":"Francesca","family":"Gay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-8001","authenticated-orcid":false,"given":"Wilfried","family":"Roeloffzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2534-9239","authenticated-orcid":false,"given":"Laura","family":"Rosi\u00f1ol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"van der Klift","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8144-541X","authenticated-orcid":false,"given":"Roberto","family":"Mina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-2221","authenticated-orcid":false,"given":"Albert","family":"Oriol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Katodritou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Lung","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Rodr\u00edguez Otero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"H\u00e1jek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Antonioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"van Duin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"D\u2019Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-0063","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena M.","family":"van Leeuwen-Segarceanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Zamagni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-2603","authenticated-orcid":false,"given":"Niels W. C. J.","family":"van de Donk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9422-6614","authenticated-orcid":false,"given":"Katja C.","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lud\u011bk","family":"Pour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Radocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Belotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-0569","authenticated-orcid":false,"given":"Fredrik","family":"Schjesvold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4563-3405","authenticated-orcid":false,"given":"Joan","family":"Blad\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-0819","authenticated-orcid":false,"given":"Hermann","family":"Einsele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-2237","authenticated-orcid":false,"given":"Pieter","family":"Sonneveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Boccadoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemiek","family":"Broijl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"4282_CR1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","volume":"32","author":"MA Dimopoulos","year":"2021","unstructured":"Dimopoulos, M. A. et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 32, 309\u2013322 (2021).","journal-title":"Ann. Oncol."},{"key":"4282_CR2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1056\/NEJMoa2312054","volume":"390","author":"P Sonneveld","year":"2024","unstructured":"Sonneveld, P. et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 390, 301\u2013313 (2024).","journal-title":"N. Engl. J. Med."},{"key":"4282_CR3","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/S1470-2045(21)00428-9","volume":"22","author":"P Moreau","year":"2021","unstructured":"Moreau, P. et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 22, 1378\u20131390 (2021).","journal-title":"Lancet Oncol."},{"key":"4282_CR4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","volume":"394","author":"P Moreau","year":"2019","unstructured":"Moreau, P. et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet 394, 29\u201338 (2019).","journal-title":"Lancet"},{"key":"4282_CR5","doi-asserted-by":"crossref","first-page":"e810","DOI":"10.1016\/S2352-3026(22)00263-0","volume":"9","author":"H Goldschmidt","year":"2022","unstructured":"Goldschmidt, H. et al. Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. Lancet Haematol. 9, e810\u2013e821 (2022).","journal-title":"Lancet Haematol."},{"key":"4282_CR6","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1200\/JCO-24-02266","volume":"43","author":"EK Mai","year":"2025","unstructured":"Mai, E. K. et al. Isatuximab, lenalidomide, bortezomib, and dexamethasone induction therapy for transplant-eligible newly diagnosed multiple myeloma: final part 1 analysis of the GMMG-HD7 trial. J. Clin. Oncol. 43, 1279\u20131288 (2025).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR7","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/S1470-2045(24)00282-1","volume":"25","author":"P Moreau","year":"2024","unstructured":"Moreau, P. et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial. Lancet Oncol. 25, 1003\u20131014 (2024).","journal-title":"Lancet Oncol."},{"key":"4282_CR8","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.clml.2019.04.018","volume":"19","author":"RZ Orlowski","year":"2019","unstructured":"Orlowski, R. Z. et al. Carfilzomib\u2013dexamethasone versus bortezomib-dexamethasone in relapsed or refractory multiple myeloma: updated overall survival, safety, and subgroups. Clin. Lymphoma Myeloma Leuk. 19, 522\u2013530.e1 (2019).","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"4282_CR9","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1016\/S1470-2045(21)00535-0","volume":"22","author":"F Gay","year":"2021","unstructured":"Gay, F. et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomized, open-label, phase 2 trial. Lancet Oncol. 22, 1705\u20131720 (2021).","journal-title":"Lancet Oncol."},{"key":"4282_CR10","unstructured":"Gay, F. et al. Carfilzomib induction, consolidation, and maintenance with or without autologous stem-cell transplant: long-term follow-up of the randomised, phase 2 FORTE trial. Hemasphere 9, 220\u2013221 abstr. S194 [EHA 2025 30th Congress] (2025)."},{"key":"4282_CR11","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1470-2045(22)00693-3","volume":"24","author":"R Mina","year":"2022","unstructured":"Mina, R. et al. Carfilzomib induction, consolidation, and maintenance with or without autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: pre-planned cytogenetic subgroup analysis of the randomised, phase 2 FORTE trial. Lancet Oncol. 24, 64\u201376 (2022).","journal-title":"Lancet Oncol."},{"key":"4282_CR12","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJMoa2400712","volume":"391","author":"T Facon","year":"2024","unstructured":"Facon, T. et al. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 391, 1597\u20131609 (2024).","journal-title":"N. Engl. J. Med."},{"key":"4282_CR13","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.1158\/1078-0432.CCR-14-0695","volume":"20","author":"J Deckert","year":"2014","unstructured":"Deckert, J. et al. SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin. Cancer Res. 20, 4574\u20134583 (2014).","journal-title":"Clin. Cancer Res."},{"key":"4282_CR14","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1158\/1078-0432.CCR-16-3192","volume":"23","author":"X Feng","year":"2017","unstructured":"Feng, X. et al. Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma. Clin. Cancer Res. 23, 4290\u20134300 (2017).","journal-title":"Clin. Cancer Res."},{"key":"4282_CR15","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/S0140-6736(21)00592-4","volume":"397","author":"P Moreau","year":"2021","unstructured":"Moreau, P. et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet 397, 2361\u20132371 (2021).","journal-title":"Lancet"},{"key":"4282_CR16","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(19)32556-5","volume":"394","author":"M Attal","year":"2019","unstructured":"Attal, M. et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet 394, 2096\u20132107 (2019).","journal-title":"Lancet"},{"key":"4282_CR17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1182\/blood.2024026230","volume":"146","author":"A Perrot","year":"2025","unstructured":"Perrot, A. et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial. Blood 146, 52\u201361 (2025).","journal-title":"Blood"},{"key":"4282_CR18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1200\/JCO.23.01696","volume":"42","author":"LB Leypoldt","year":"2024","unstructured":"Leypoldt, L. B. et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone for the treatment of high-risk newly diagnosed multiple myeloma. J. Clin. Oncol. 42, 26\u201337 (2024).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR19","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1056\/NEJMoa2505133","volume":"393","author":"A Perrot","year":"2025","unstructured":"Perrot, A. et al. Measurable residual disease-guided therapy in newly diagnosed myeloma. N. Engl. J. Med. 393, 425\u2013437 (2025).","journal-title":"N. Engl. J. Med."},{"key":"4282_CR20","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1200\/JCO.2016.69.2517","volume":"35","author":"J-J Lahuerta","year":"2017","unstructured":"Lahuerta, J.-J. et al. Depth of response in multiple myeloma: a pooled analysis of three PETHEMA\/GEM clinical trials. J. Clin. Oncol. 35, 2900\u20132910 (2017).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR21","doi-asserted-by":"crossref","first-page":"5988","DOI":"10.1182\/bloodadvances.2020002827","volume":"4","author":"NC Munshi","year":"2020","unstructured":"Munshi, N. C. et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv. 4, 5988\u20135999 (2020).","journal-title":"Blood Adv."},{"key":"4282_CR22","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1182\/blood.2024024371","volume":"144","author":"O Landgren","year":"2024","unstructured":"Landgren, O. et al. EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma. Blood 144, 359\u2013367 (2024).","journal-title":"Blood"},{"key":"4282_CR23","unstructured":"Center for Drug Evaluation and Research April 12, 2024 Meeting of the Oncologic Drugs Advisory Committee (ODAC) Webcast\u2014Part 2 (U.S. Food and Drug Administration, 2024); https:\/\/www.fda.gov\/media\/177651\/download"},{"key":"4282_CR24","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1182\/blood-2012-04-422683","volume":"120","author":"AJ Jakubowiak","year":"2012","unstructured":"Jakubowiak, A. J. et al. A phase 1\/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood 120, 1801\u20131809 (2012).","journal-title":"Blood"},{"key":"4282_CR25","doi-asserted-by":"crossref","unstructured":"Jakubowiak, A. J. et al. Treatment outcome with the combination of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) for newly diagnosed multiple myeloma (NDMM) after extended follow-up. J. Clin. Oncol. 31, abstr. 8543 [ASCO 2013 Annual Meeting] (2013).","DOI":"10.1200\/jco.2013.31.15_suppl.8543"},{"key":"4282_CR26","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1200\/JCO-24-01893","volume":"43","author":"H Avet-Loiseau","year":"2025","unstructured":"Avet-Loiseau, H. et al. International Myeloma Society\/International Myeloma working group consensus recommendations on the definition of high-risk multiple myeloma. J. Clin. Oncol. 43, 2739\u20132751 (2025).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR27","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1200\/JCO.19.01231","volume":"38","author":"B Paiva","year":"2020","unstructured":"Paiva, B. et al. Measurable residual disease by next-generation flow cytometry in multiple myeloma. J. Clin. Oncol. 38, 784\u2013792 (2020).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR28","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/s41375-020-0711-6","volume":"34","author":"NJ Bahlis","year":"2020","unstructured":"Bahlis, N. J. et al. Daratumumab plus lenalidomide and dexamethasone in relapsed\/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia 34, 1875\u20131884 (2020).","journal-title":"Leukemia"},{"key":"4282_CR29","doi-asserted-by":"crossref","unstructured":"Costa, L. J. et al. International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials. Leukemia 35, 18\u201330 (2021).","DOI":"10.1038\/s41375-020-01012-4"},{"key":"4282_CR30","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1182\/blood-2018-06-858613","volume":"132","author":"A Perrot","year":"2018","unstructured":"Perrot, A. et al. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood 132, 2456\u20132464 (2018).","journal-title":"Blood"},{"key":"4282_CR31","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1200\/JCO.21.01935","volume":"40","author":"LJ Costa","year":"2022","unstructured":"Costa, L. J. et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma. J. Clin. Oncol. 40, 2901\u20132912 (2022).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR32","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1182\/blood.2020005288","volume":"136","author":"PM Voorhees","year":"2020","unstructured":"Voorhees, P. M. et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood 136, 936\u2013945 (2020).","journal-title":"Blood"},{"key":"4282_CR33","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1200\/JCO.22.02567","volume":"41","author":"MF Kaiser","year":"2023","unstructured":"Kaiser, M. F. et al. Daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone as induction and extended consolidation improves outcome in ultra-high-risk multiple myeloma. J. Clin. Oncol. 41, 3945\u20133955 (2023).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR34","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1182\/blood.2023022080","volume":"143","author":"M D\u2019Agostino","year":"2024","unstructured":"D\u2019Agostino, M. et al. Predictors of unsustained measurable residual disease negativity in patients with multiple myeloma. Blood 143, 592\u2013596 (2024).","journal-title":"Blood"},{"key":"4282_CR35","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1182\/blood.2023022083","volume":"143","author":"C Guerrero","year":"2024","unstructured":"Guerrero, C. et al. Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma. Blood 143, 597\u2013603 (2024).","journal-title":"Blood"},{"key":"4282_CR36","doi-asserted-by":"crossref","unstructured":"Zamagni, E. et al. Phase 3 study of teclistamab (Tec) in combination with lenalidomide (Len) and Tec alone versus Len alone in newly diagnosed multiple myeloma (NDMM) as maintenance therapy following autologous stem cell transplantation (ASCT): safety run-in (SRI) results from the Majestec-4\/EMN30 Trial. Blood 144, abstr. 494 [ASH 2024 66th Meeting] (2024).","DOI":"10.1182\/blood-2024-205608"},{"key":"4282_CR37","doi-asserted-by":"crossref","unstructured":"Broijl, A. et al. EMAGINE\/CARTITUDE-6: a randomized phase 3 study of DVRd followed by ciltacabtagene autoleucel versus DVRd followed by autologous stem cell transplant in transplant-eligible patients with newly diagnosed multiple myeloma. Hemasphere 7, 22\u201323, abstr. P23 [EHA 2023 28th Congress] (2023).","DOI":"10.1097\/01.HS9.0000936220.68605.8b"},{"key":"4282_CR38","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.3324\/haematol.2014.117176","volume":"100","author":"E Terpos","year":"2015","unstructured":"Terpos, E. et al. European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica 100, 1254\u20131266 (2015).","journal-title":"Haematologica"},{"key":"4282_CR39","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1038\/s41375-020-0876-z","volume":"34","author":"E Terpos","year":"2020","unstructured":"Terpos, E. et al. Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN). Leukemia 34, 2000\u20132011 (2020).","journal-title":"Leukemia"},{"key":"4282_CR40","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/s41375-023-01920-1","volume":"37","author":"E Terpos","year":"2023","unstructured":"Terpos, E. et al. Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN). Leukemia 37, 1175\u20131185 (2023).","journal-title":"Leukemia"},{"key":"4282_CR41","unstructured":"NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae). Multiple Myeloma. Version 4.2025 \u2014 November 26, 2025 (National Comprehensive Cancer Network, 2025)."},{"key":"4282_CR42","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1200\/JCO-25-00744","volume":"43","author":"S Ailawadhi","year":"2025","unstructured":"Ailawadhi, S. et al. Isatuximab subcutaneous by on-body injector versus isatuximab intravenous plus pomalidomide and dexamethasone in relapsed\/refractory multiple myeloma: phase III IRAKLIA study. J. Clin. Oncol. 43, 2527\u20132537 (2025).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR43","doi-asserted-by":"crossref","first-page":"e890","DOI":"10.1016\/S2352-3026(23)00236-3","volume":"10","author":"LJ Costa","year":"2023","unstructured":"Costa, L. J. et al. Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial. Lancet Haematol. 10, e890\u2013e901 (2023).","journal-title":"Lancet Haematol."},{"key":"4282_CR44","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41375-021-01431-x","volume":"36","author":"LB Leypoldt","year":"2022","unstructured":"Leypoldt, L. B. et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial. Leukemia 36, 885\u2013888 (2022).","journal-title":"Leukemia"},{"key":"4282_CR45","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","volume":"15","author":"SV Rajkumar","year":"2014","unstructured":"Rajkumar, S. V. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 15, e538\u2013e548 (2014).","journal-title":"Lancet Oncol."},{"key":"4282_CR46","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1200\/JCO.2005.04.242","volume":"23","author":"PR Greipp","year":"2005","unstructured":"Greipp, P. R. et al. International staging system for multiple myeloma. J. Clin. Oncol. 23, 3412\u20133420 (2005).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR47","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1182\/blood-2016-01-631200","volume":"127","author":"P Sonneveld","year":"2016","unstructured":"Sonneveld, P. et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood 127, 2955\u20132962 (2016).","journal-title":"Blood"},{"key":"4282_CR48","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","volume":"33","author":"A Palumbo","year":"2015","unstructured":"Palumbo, A. et al. Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J. Clin. Oncol. 33, 2863\u20132869 (2015).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR49","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1200\/JCO.21.02614","volume":"364","author":"M D\u2019Agostino","year":"2022","unstructured":"D\u2019Agostino, M. et al. Second Revision of the International Staging System (R2-ISS) for overall survival in multiple myeloma: a European Myeloma Network (EMN) report within the HARMONY project. J. Clin. Oncol. 364, 3406\u20133418 (2022).","journal-title":"J. Clin. Oncol."},{"key":"4282_CR50","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1016\/S1470-2045(16)30206-6","volume":"17","author":"S Kumar","year":"2016","unstructured":"Kumar, S. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 17, e328\u2013e346 (2016).","journal-title":"Lancet Oncol."},{"key":"4282_CR51","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.1182\/blood-2012-07-444042","volume":"120","author":"M Faham","year":"2012","unstructured":"Faham, M. et al. Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia. Blood 120, 5173\u20135180 (2012).","journal-title":"Blood"},{"key":"4282_CR52","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/14737159.2019.1627877","volume":"19","author":"A Monter","year":"2019","unstructured":"Monter, A. & Nomded\u00e9u, J. F. ClonoSEQ assay for the detection of lymphoid malignancies. Expert Rev. Mol. Diagn. 19, 571\u2013578 (2019).","journal-title":"Expert Rev. Mol. Diagn."},{"key":"4282_CR53","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1038\/leu.2017.29","volume":"31","author":"J Flores-Montero","year":"2017","unstructured":"Flores-Montero, J. et al. Next generation flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia 31, 2094\u20132103 (2017).","journal-title":"Leukemia"},{"key":"4282_CR54","unstructured":"clonoSEQ\u00ae Assay Technical Information (Adaptive Biotechnologies Corporation, 2021); https:\/\/ous.clonoseq.com\/technical-documents\/"},{"key":"4282_CR55","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (US Dept of Health and Human Services, National Institutes of Health, National Cancer Institute, 2017); https:\/\/dctd.cancer.gov\/research\/ctep-trials\/for-sites\/adverse-events\/ctcae-v5-5x7.pdf"},{"key":"4282_CR56","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","volume":"42","author":"PA Harris","year":"2009","unstructured":"Harris, P. A. et al. Research electronic data capture (REDCap)\u2014a metadata-driven methodology and workflow process for providing translational research informatics support. J. Biomed. Inform. 42, 377\u2013381 (2009).","journal-title":"J. Biomed. Inform."},{"key":"4282_CR57","doi-asserted-by":"crossref","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","volume":"95","author":"PA Harris","year":"2019","unstructured":"Harris, P. A. et al. The REDCap consortium: building an international community of software platform partners. J. Biomed. Inform. 95, 103208 (2019).","journal-title":"J. Biomed. Inform."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04282-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04282-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04282-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:02:48Z","timestamp":1779285768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04282-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":57,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["4282"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04282-0","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"27 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the version of this article initially published, Joan Blad\u00e9 (Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Cl.nic de Barcelona, IDIBAPS, and PETHEMA\/GEM, Barcelona, Spain) was listed with an incorrect affiliation which is now amended in the HTML and PDF versions of the article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors report the following competing interests. F.G. reported receiving honoraria from Amgen, Janssen, Takeda, Sanofi, Bristol Myers Squibb\/Celgene, AbbVie, Pfizer and GlaxoSmithKline and serving on the advisory boards for Amgen, Janssen, Takeda, Pfizer, Sanofi, Bristol Myers Squibb\/Celgene, Oncopeptides, Roche, AbbVie, GlaxoSmithKline, AstraZeneca, Regeneron and Gilead\/Kite. W.R. reported receiving (not personal) honoraria from Janssen, Bristol Myers Squibb\/Celgene and Genzyme and receiving contributions for travel and accommodation expenses from Janssen and AbbVie. M.A.D. reported receiving honoraria for participation in advisory boards and satellite symposia from Amgen, Sanofi, Regeneron, Menarini, Takeda, GlaxoSmithKline, Bristol Myers Squibb, Janssen, BeiGene, Swixx and AstraZeneca. L.R. reported receiving honoraria for lectures and participation in advisory boards from Janssen, Bristol Myers Squibb, Amgen, Sanofi, GlaxoSmithKline and Menarini. R.M. reported receiving honoraria from Janssen, Pfizer, Sanofi, AbbVie, Regeneron, Bristol Myers Squibb, Takeda and Amgen; serving on the advisory boards for Janssen, Pfizer, Sanofi, Takeda, Bristol Myers Squibb and Amgen; and receiving consultancy fees from Janssen, Pfizer and Sanofi. A.O. reported receiving honoraria for participation in advisory boards and sponsored symposiums from Sanofi, Janssen, Bristol Myers Squibb, GlaxoSmithKline, Pfizer and Amgen. E.K. reported receiving honoraria from and serving on the advisory boards for Janssen, GlaxoSmithKline, Sanofi, Takeda, Amgen, Pfizer and AbbVie and receiving contributions to clinical research from Janssen, Karyopharm, AbbVie, Sanofi, GlaxoSmithKline, Amgen, Pfizer and Prothena Biosciences. K.L.W. reported receiving consultancy fees from Janssen, Takeda and Sanofi. P.R.O. reported receiving honoraria from Amgen, Celgene\/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Regeneron, Sanofi and AbbVie; serving on the advisory boards for Janssen, Oncopeptides, H3Biomedicina, GlaxoSmithKline, Pfizer, Sanofi, Bristol Myers Squibb, Roche and Regeneron; receiving consultancy fees from Roche, Pfizer, AbbVie and Bristol Myers Squibb; and being a member of steering committees for Regeneron, Janssen and Bristol Myers Squibb. R.H. reported having a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, Bristol Myers Squibb, Novartis, PharmaMar and Takeda; receiving honoraria from Janssen, Amgen, Celgene, Bristol Myers Squibb, PharmaMar and Takeda; receiving research funding from Janssen, Amgen, Celgene, Bristol Myers Squibb, Novartis and Takeda; serving on the advisory boards for Bristol Myers Squibb, Takeda, Amgen, Oncopeptides, Sanofi, Janssen and GlaxoSmithKline; and receiving support for attending meetings and\/or travel from Amgen, Celgene, Takeda and Janssen. E.A. reported receiving honoraria from Sanofi and serving on the advisory boards for Janssen, Takeda, Amgen, Pfizer, Menarini and GlaxoSmithKline. M.D. reported receiving honoraria from GlaxoSmithKline, Sanofi and Janssen; serving on the advisory boards for GlaxoSmithKline, Sanofi, Bristol Myers Squibb, Janssen and Adaptive Biotechnologies; and receiving research support from Janssen. J.M.-L. reported serving on the advisory boards for Sanofi, Janssen, Bristol Myers Squibb, Amgen, Kite and Roche. E.Z. reported receiving honoraria from and serving on the advisory boards for Bristol Myers Squibb, Janssen, Amgen, Pfizer, Oncopeptides, Menarini-Stemline and Sanofi. N.W.C.J.v.D.D. reported receiving research support from Janssen Pharmaceuticals, Amgen, Celgene, CellCentric, Novartis, Cellectis and Bristol Myers Squibb and serving on the advisory boards for Janssen Pharmaceuticals, Amgen, Celgene, Bristol Myers Squibb, Sanofi, Takeda, Roche, Novartis, Bayer, Adaptive Biotechnologies, Galapagos, Kite Pharma, Merck, Pfizer, AbbVie and Servier, all paid to the institution. K.C.W. reported receiving research grants to her institution from AbbVie, Amgen, Bristol Myers Squibb\/Celgene, GlaxoSmithKline, Janssen and Sanofi; receiving research grants from Pfizer and Takeda; receiving honoraria from AbbVie, Amgen, Adaptive Biotechnologies, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Janssen, GlaxoSmithKline, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Roche Pharma, Sanofi, Stemline and Takeda; and serving on the advisory boards for AbbVie, Amgen, Adaptive Biotechnologies, BeiGene, Bristol Myers Squibb, Celgene, Janssen, GlaxoSmithKline, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Regeneron, Roche Pharma, Sanofi and Takeda. J.R. reported receiving honoraria from and serving on the advisory boards for Johnson & Johnson, Sanofi, Amgen, Pfizer, Bristol Myers Squibb, Janssen, Sanofi and GlaxoSmithKline; and receiving travel reimbursements from Johnson & Johnson and Sanofi. A. Belotti reported serving on the advisory boards for Amgen, Pfizer, Janssen, GlaxoSmithKline and Menarini Stemline. F.S. reported receiving honoraria from Amgen, Bristol Myers Squibb, Takeda, AbbVie, Janssen, Oncopeptides, Sanofi, GlaxoSmithKline, Menarini and Regeneron and serving on the advisory boards for AbbVie, Bristol Myers Squibb, Oncopeptides, GlaxoSmithKline, Janssen, Sanofi and Takeda. J.B. reported receiving honoraria for lectures from Janssen, Amgen, Celgene\/Bristol Myers Squibb and Sanofi. H.E. reported having a consulting or advisory role for Bristol Myers Squibb\/Celgene, Janssen, Amgen, Takeda, Sanofi, GlaxoSmithKline, Novartis and Roche; receiving research funding from Bristol Myers Squibb\/Celgene, Janssen, Amgen, GlaxoSmithKline, Sanofi and Novartis; receiving honoraria from Bristol Myers Squibb\/Celgene, Janssen, Amgen, Takeda, Sanofi, GlaxoSmithKline, Novartis and Roche; and receiving travel support from Bristol Myers Squibb\/Celgene, Janssen, Amgen and Sanofi. P.S. reported receiving research funding from Amgen, Bristol Myers Squibb, Celgene, Janssen and Karyopharm and serving on the advisory boards for Amgen, Bristol Myers Squibb, Celgene, Janssen, Karyopharm and Pfizer. M.B. reported receiving honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb and AbbVie; serving on the advisory boards for Janssen and GlaxoSmithKline and receiving research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb and Mundipharma. A. Broijl reported receiving honoraria from and serving on the advisory boards for Janssen, Sanofi, Bristol Myers Squibb and Amgen. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}