{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:53:52Z","timestamp":1790409232268,"version":"4.1.0"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"11","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,4,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Newly approved drugs and combinations treating multiple myeloma (MM) have resulted in substantial improvements in patients' survival. To deliver rapid access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to evaluate the minimal residual disease\u2013negative complete response (MRD-CR) as an intermediate end point for progression-free survival (PFS) and overall survival (OS) in newly diagnosed (ND) transplant-eligible (NDTE) patients, ND transplant-ineligible (NDTinE) patients, and patients with relapsed\/refractory (RR) MM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      Individual patient data from 20 randomized multicenter trials were collected. Eleven studies (4,773 patients) with sufficient data were analyzed to evaluate whether 9- or 12-month MRD-CR classified at a 10\n                      <jats:sup>\u20135<\/jats:sup>\n                      threshold could be reasonably likely to predict the clinical benefit of new agents regarding PFS and OS. Global odds ratio (OR) was estimated using the bivariate Plackett Copula model. Supportive evaluation included correlations of the treatment effects on MRD-CR end points and PFS\/OS, evaluated by both linear regression (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>weighted least squared<\/jats:sub>\n                      ) and Copula (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>Copula<\/jats:sub>\n                      ) models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The analysis demonstrated that both 9- and 12-month MRD-CR strongly correlated with PFS at patient level in NDTE patients, NDTinE patients, and patients with RRMM. Global ORs ranged from 3.06 to 16.24, all with 95% CIs excluding 1.0. Encouraging trial-level correlations (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      , 0.61-0.70) were observed by pooling three populations and were stronger (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      , 0.67-0.78) in the ND population. Similar results were observed for OS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Our findings provided the support for use of MRD-CR classified at a 10\n                      <jats:sup>\u20135<\/jats:sup>\n                      threshold at either 9 or 12 months after starting of the treatment, as an intermediate end point to support accelerated approvals, in future trials in NDTE patients, NDTinE patients, and patients with RRMM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-24-02020","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T15:59:16Z","timestamp":1739375956000},"page":"1289-1301","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":45,"title":["Minimal Residual Disease\u2013Based End Point for Accelerated Assessment of Clinical Trials in Multiple Myeloma: A Pooled Analysis of Individual Patient Data From Multiple Randomized Trials"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-8832","authenticated-orcid":true,"given":"Qian","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-3815","authenticated-orcid":true,"given":"Bruno","family":"Paiva","sequence":"additional","affiliation":[{"name":"Department of Hematology and Immunology, University of Navara, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5902-8882","authenticated-orcid":true,"given":"Levi D.","family":"Pederson","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Dimier","sequence":"additional","affiliation":[{"name":"Roche Products Limited, St Albans, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ela","family":"Talpes","sequence":"additional","affiliation":[{"name":"Amgen Inc, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5220-7730","authenticated-orcid":true,"given":"Thomas J.","family":"Prior","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Inc, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":true,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-8746","authenticated-orcid":false,"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Hotel-dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-2237","authenticated-orcid":true,"given":"Pieter","family":"Sonneveld","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-9284","authenticated-orcid":true,"given":"Shaji K.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse G.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reshma","family":"Patel","sequence":"additional","affiliation":[{"name":"Johnson &amp; 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