{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:48:28Z","timestamp":1790822908301,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This analysis describes the pharmacokinetic\/pharmacodynamic (PK\/PD) modeling framework that supported selection of the isatuximab (anti\u2010CD38 monoclonal antibody) dosing regimen alongside its early clinical development in patients with relapsed\/refractory multiple myeloma (RRMM). The PK\/PD mathematical model characterized the variations of patient serum M\u2010protein concentrations, the primary marker of tumor burden in multiple myeloma (MM). Three separate PK\/PD models were built sequentially as data became available from phase I clinical trials. The primary PK\/PD analysis was initiated using monotherapy phase I study data (\n                    <jats:italic>n<\/jats:italic>\n                    = 122), followed by analysis of data collected from phase Ib combination studies with lenalidomide and dexamethasone (Rd,\n                    <jats:italic>n<\/jats:italic>\n                    = 40) and then with pomalidomide and dexamethasone (Pd,\n                    <jats:italic>n<\/jats:italic>\n                    = 31). Using the PK\/PD model, abnormal \u201cmyeloma\u201d protein (M\u2010protein) profiles under different isatuximab dosing regimens were simulated. Overall, simulations revealed that regimens which included a loading period of four weekly administrations followed by administration every 2 weeks thereafter (QW4\u2010Q2W), reduced M\u2010protein levels more than a Q2W regimen without a loading period. For isatuximab monotherapy, a 20\u00a0mg\/kg dose induced greater reduction in serum M\u2010protein levels compared with doses equal or lower than 10\u00a0mg\/kg. For isatuximab in combination with either Rd or Pd, simulations yielded no substantial benefit in terms of M\u2010protein reduction between isatuximab 10\u00a0mg\/kg and 20\u00a0mg\/kg. These PK\/PD analyses supported the use of isatuximab 10\u00a0mg\/kg QW4\u2010Q2W in combination with Pd in the phase III trial.\n                  <\/jats:p>","DOI":"10.1002\/psp4.12666","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T18:36:40Z","timestamp":1624991800000},"page":"928-940","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["PK\/PD modeling analysis for dosing regimen selection of isatuximab as single agent and in combination therapy in patients with multiple myeloma"],"prefix":"10.1002","volume":"10","author":[{"given":"Kimiko","family":"Koiwai","sequence":"first","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raouf","family":"El\u2010Cheikh","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoai\u2010Thu","family":"Thai","sequence":"additional","affiliation":[{"name":"Sanofi Data and Data Sciences Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-3211","authenticated-orcid":false,"given":"Claire","family":"Brillac","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Baptiste","family":"Fau","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Veyrat\u2010Follet","sequence":"additional","affiliation":[{"name":"Sanofi Data and Data Sciences Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Laure","family":"Risse","sequence":"additional","affiliation":[{"name":"Sanofi Oncology Vitry\u2010sur\u2010Seine France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helgi","family":"van de Velde","sequence":"additional","affiliation":[{"name":"Sanofi Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doroth\u00e9e","family":"Semiond","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; 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