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Serum M\u2010protein levels and PFS data from 203 evaluable patients, included either in a phase I\/II study (<jats:italic>n<\/jats:italic>\u2009=\u2009173) or in a phase I study (<jats:italic>n<\/jats:italic>\u2009=\u200930), were used to build the model. First, we independently developed a longitudinal model and a PFS model. Then, we linked them in a nonlinear joint model by selecting the link function that best captured the association between serum M\u2010protein kinetics and PFS. A Claret tumor growth\u2010inhibition model accounting for the additive effects of Isa, with an <jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub> function, Pom, and Dex on serum M\u2010protein elimination was selected to describe serum M\u2010protein kinetics. PFS was best described with a log\u2010logistic model and associations with baseline beta\u20102 microglobulin level, age, and coadministration of Dex were identified. The instantaneous change in serum M\u2010protein level was found to be associated with PFS in the final joint model. Using model simulations, we retrospectively supported the Isa 10\u2009mg\/kg weekly for 4\u2009weeks, then biweekly (QW\/Q2W) dosing regimen of the ICARIA\u2010MM phase III pivotal study, and validated it using the same phase III pivotal study data.<\/jats:p>","DOI":"10.1002\/psp4.13206","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T17:40:46Z","timestamp":1732815646000},"page":"2087-2101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Isatuximab\u2013dexamethasone\u2013pomalidomide combination effects on serum M protein and <scp>PFS<\/scp> in myeloma: Development of a joint model using phase I\/<scp>II<\/scp> data"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0428-2300","authenticated-orcid":false,"given":"Antoine","family":"Pitoy","sequence":"first","affiliation":[{"name":"Sanofi Data and Data Sciences Translational Disease Modeling  Gentilly France"},{"name":"INSERM, SPHERE, U1246 Tours University, Nantes University  Tours France"},{"name":"INSERM, IAME Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol\u00e8ne","family":"Desm\u00e9e","sequence":"additional","affiliation":[{"name":"INSERM, SPHERE, U1246 Tours University, Nantes University  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Riglet","sequence":"additional","affiliation":[{"name":"Sanofi Data and Data Sciences Translational Disease Modeling  Gentilly France"},{"name":"INSERM, IAME Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Clinical Pharmacometrics, Quantitative Pharmacology Servier  Saclay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-6399","authenticated-orcid":false,"given":"Hoai\u2010Thu","family":"Thai","sequence":"additional","affiliation":[{"name":"Sanofi Data and Data Sciences Translational Disease Modeling  Gentilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zandra","family":"Klippel","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine and Early Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doroth\u00e9e","family":"Semiond","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine and Early Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9865-8959","authenticated-orcid":false,"given":"Christine","family":"Veyrat\u2010Follet","sequence":"additional","affiliation":[{"name":"Sanofi Data and Data Sciences Translational Disease Modeling  Gentilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6568-1041","authenticated-orcid":false,"given":"Julie","family":"Bertrand","sequence":"additional","affiliation":[{"name":"INSERM, IAME Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60493-1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041875"},{"key":"e_1_2_11_4_1","unstructured":"World Health Organization.Global cancer observatory. 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