{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:19:51Z","timestamp":1785550791442,"version":"3.56.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Patients with multiple myeloma often require multiple treatment lines. The order in which treatments are sequenced has impact on clinical outcomes. This study aimed to estimate progression\u2010free survival (PFS) and overall survival (OS) with common treatment sequences used in Portugal and the incremental benefit of an optimal sequence in transplant\u2010ineligible patients with multiple myeloma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A state\u2010transition sequential model with a five\u2010health state conceptual structure was developed to simulate and compare survival outcomes between treatment sequences up to four lines of treatments. Data sources included randomized clinical trials and indirect treatment comparisons. A panel of Portuguese hematologists listed four most common treatment sequences and optimal sequence of choice in transplant\u2010ineligible patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our simulation estimated an OS between 6.1 and 7.8\u2009years using the most common sequences, with VMP\u2009+\u2009DRd\u2009+\u2009Pd\u2009+\u2009Kd as the most effective (7.8\u2009years). Optimal sequence of choice (DRd\u2009+\u2009PVd\u2009+\u2009Kd\u2009+\u2009Vd) achieved OS of 9.8\u2009years and may extend OS in 2.0\u20133.7\u2009years vs. most common sequences (26%\u201361% increase). This benefit was mostly explained by extended PFS in the first line of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Model results demonstrate that choosing the most effective treatment upfront is crucial in delaying disease progression thus yielding better survival outcomes in transplant\u2010ineligible patients. There was a clear survival benefit in using daratumumab\u2010based regimens in first line. This modelling exercise highlights the need to raise awareness around the impact of sequencing strategies to improve patient's outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.70027","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T06:34:04Z","timestamp":1728369244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Improving Health Outcomes Through Treatment Sequencing Optimization in Multiple Myeloma: A Simulation Model in Transplant\u2010Ineligible Patients"],"prefix":"10.1002","volume":"7","author":[{"given":"C.","family":"Geraldes","sequence":"first","affiliation":[{"name":"Centro Hospitalar Universit\u00e1rio de Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Neves","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Champalimaud  Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Bergantim","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal; i3S \u2010 Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Hematology Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5079-1677","authenticated-orcid":false,"given":"C.","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute for Evidence\u2010Based Health (ISBE)  Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Leal\u00a0da\u00a0Costa","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia  Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-020-00993-5"},{"key":"e_1_2_12_3_1","unstructured":"GLOBOCAN \u201cInternational Agency for Research on Cancer [Online] \u201d2020 https:\/\/gco.iarc.fr\/today\/online\u2010analysis\u2010table."},{"issue":"1","key":"e_1_2_12_4_1","first-page":"3","article-title":"Epidemiology, Staging, and Management of Multiple Myeloma","volume":"9","author":"Padala S. 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