{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T19:51:44Z","timestamp":1792957904337,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["Bristol-Myers Squibb"],"award-info":[{"award-number":["Bristol-Myers Squibb"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Patient Rep Outcomes"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Here we aim to evaluate the relationship between progression-free survival (PFS) and patient-reported symptoms (measured by health-related quality of life scores) among patients with relapsed\/refractory multiple myeloma (RRMM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Pain and fatigue were identified as the most common patient-relevant symptoms within RRMM based on a predefined literature review of patient preference\/qualitative studies (confirmed by clinical experts). Consequently, the European Organisation for Research and Treatment of Cancer QLQ-C30 pain, QLQ-MY20 disease symptoms (pain in different locations), and QLQ-C30 fatigue domains were selected. Change from baseline scores per symptom domain was jointly modeled with PFS assuming a current slope association structure. For each symptom, we evaluated trial-specific joint models based on individual patient data from 7 RRMM clinical trials. The association between symptoms and PFS was summarized via association-effect hazard ratios (HRs) from the joint models, where a HR\u2009&gt;\u20091 indicates that symptom worsening was associated with an increased hazard of a progression\/death event. Meta-analyses were performed to synthesize the joint model HRs from all trials into one summary statistic (meta-HR) per symptom domain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across trials, worsening in pain and fatigue was associated with an increased hazard of progression events (disease progression\/death) based on joint-model-association-effect HRs. Specifically, meta-HRs (95% CI) were 1.10 (1.02, 1.19) for QLQ-C30 pain, 1.10 (1.01, 1.20) for QLQ-MY20 disease symptoms, and 1.11 (1.05, 1.17) for QLQ-C30 fatigue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated that worsening in pain and fatigue was consistently associated with an increased hazard of disease progression or death events across numerous RRMM clinical trials with varying disease severity. This suggests risk of PFS events may align with patient experience in terms of worsening symptom burden.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41687-025-00943-9","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T09:48:31Z","timestamp":1760435311000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Joint modeling of progression-free survival and patient-reported outcomes to evaluate the association between disease progression and symptoms among patients with relapsed\/refractory multiple myeloma"],"prefix":"10.1186","volume":"9","author":[{"given":"Stefan","family":"Knop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Einsele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devender","family":"Dhanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Eliason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"McLoone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde","family":"Caisip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny M. 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HE reports consulting fees and honoraria from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Roche, Sanofi, and Takeda; participation on a Data Safety Monitoring Board or Advisory Board from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Roche, Sanofi, and Takeda; and support for attending meetings from Amgen, Bristol Myers Squibb, Janssen, and Sanofi. KR reports honoraria from Adaptive Biotechnologies, AbbVie, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Oncopeptides, Pfizer, Recordati, Stemline Therapeutics, and Takeda; participation on a Data Safety Monitoring Board or Advisory Board for Adaptive Biotechnologies, AbbVie, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Oncopeptides, Pfizer, Recordati, Stemline Therapeutics, and Takeda; support for attending meetings from Amgen, Bristol Myers Squibb, Recordati, and Takeda; and institution grant funding from Bristol Myers Squibb, GlaxoSmithKline, and Sanofi. DD, TS, LE, DB, and ADD are employees of Bristol Myers Squibb. DM, CC, JMHC, SC, and KT are employees of Precision AQ, a consulting firm that received funding from Bristol Myers Squibb for this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"118"}}