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As predicting progression may allow early switching to next\u2010line therapy while the disease burden is relatively low, we evaluated the predictive accuracy of a mathematical model to anticipate relapse 180 days before the FPC is met. A subset of 470\/1143 patients from the IA16 dataset who were initially treated with VRd (Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone) in the CoMMpass study (NCT01454297) were randomly split 2:1 into training and testing sets. A model of M\u2010protein dynamics was developed using the training set and used to predict relapse probability in patients in the testing set given their response histories up to 12 or more months of treatment. The predictive accuracy of this model and M\u2010protein \u201cvelocity\u201d were assessed via receiver operating characteristics (ROC) analysis. The final model was a two\u2010population tumor growth inhibition model with additive drug effect and transit delay compartments for cell killing. The ROC area under the curve value of relapse prediction 180 days ahead of observed relapse by FPC was 0.828 using at least 360 days of response data, which was superior to the M\u2010protein velocity ROC score of 0.706 under the same conditions. The model can predict future relapse from early M\u2010protein responses and can be used in a future clinical trial to test whether early switching to second\u2010line therapy results in better outcomes in MM.<\/jats:p>","DOI":"10.1002\/psp4.13225","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T18:40:52Z","timestamp":1726598452000},"page":"2124-2136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modeling serum M\u2010protein response for early detection of biochemical relapse in myeloma patients treated with bortezomib, lenalidomide and dexamethasone"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-8776","authenticated-orcid":false,"given":"Yuki","family":"Otani","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacometrics and Systems Pharmacology, Keio Frontier Research and Education Collaboration Square (K\u2010FRECS) at Tonomachi Keio University  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7959-4969","authenticated-orcid":false,"given":"Yunqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc. 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