{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T01:40:44Z","timestamp":1787708444831,"version":"build-2784847793"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T00:00:00Z","timestamp":1670630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Use of surrogate end\u2010points such as progression\u2010free survival (PFS) and other time\u2010to\u2010event (TTE) end\u2010points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end\u2010points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary\/co\u2010primary end\u2010point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38\u20130.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30\u20130.84). In relapsed\/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42\u20130.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.<\/jats:p>","DOI":"10.1111\/bjh.18568","type":"journal-article","created":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T16:01:20Z","timestamp":1670688080000},"page":"587-594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Time\u2010to\u2010event surrogate end\u2010points in multiple myeloma randomised trials from 2005 to 2019: A surrogacy analysis"],"prefix":"10.1111","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8308-0373","authenticated-orcid":false,"given":"Tommy","family":"Etekal","sequence":"first","affiliation":[{"name":"Department of Radiation Sciences Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Koehn","sequence":"additional","affiliation":[{"name":"Division of Hematological Malignancies and Cellular Therapeutics University of Kansas  Lawrence Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas W.","family":"Sborov","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hematological Malignancies University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"McClune","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hematological Malignancies University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Prasad","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-3978","authenticated-orcid":false,"given":"Alyson","family":"Haslam","sequence":"additional","affiliation":[{"name":"Department of Epidemiology\/Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Berger","sequence":"additional","affiliation":[{"name":"Patient Advocate University of Hartford  West Hartford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Booth","sequence":"additional","affiliation":[{"name":"Division of Cancer Care and Epidemiology Queen's University Cancer Research Institute  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-8042","authenticated-orcid":false,"given":"Samer","family":"Al Hadidi","sequence":"additional","affiliation":[{"name":"Myeloma Institute The University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Al\u2010Ola","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Division of Hematological Malignancies and Cellular Therapeutics University of Kansas  Lawrence Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Goodman","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-783X","authenticated-orcid":false,"given":"Ghulam Rehman","family":"Mohyuddin","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hematological Malignancies University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2018.8351"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01050-w"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2016.10.008"},{"key":"e_1_2_10_5_1","unstructured":"FDA grants accelerated approval to melphalan flufenamide for relapsed or refractory multiple myeloma.2021;https:\/\/www.fda.gov\/drugs\/drug\u2010approvals\u2010and\u2010databases\/fda\u2010grants\u2010accelerated\u2010approval\u2010melphalan\u2010flufenamide\u2010relapsed\u2010or\u2010refractory\u2010multiple\u2010myeloma. 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