{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:29:22Z","timestamp":1791656962581,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Isatuximab, a monoclonal antibody (mAb) of immunoglobulin G (IgG) isotype, specifically targets the cluster of differentiation 38 antigen overexpressed in malignant plasma cells. Isatuximab is used to treat multiple myeloma (MM), characterized by the excessive production of abnormal \u201cmyeloma proteins\u201d (M\u2010proteins) that may interact with therapeutic IgG mAb on the neonatal Fc receptor (FcRn)\u2010mediated recycling pathway. The clinical pharmacology profile of isatuximab was investigated by population pharmacokinetics (PKs) modeling in 476 patients with MM who received 1\u201320\u00a0mg\/kg isatuximab either as single agent or in combination with pomalidomide\u2010dexamethasone in 4 clinical trials. Isatuximab PKs were characterized by a two\u2010compartment model with parallel time\u2010varying linear clearance (CL) and nonlinear elimination. Due to a mechanism\u2010based drug\u2010disease interaction, patients secreting IgG M\u2010protein exhibited a twofold lower drug exposure compared with patients with non\u2010IgG MM. No dose adjustment was required based on MM immunoglobulin type because efficacy and safety profiles were comparable between IgG and non\u2010IgG MM subpopulations. \u03b22\u2010microglobulin, body weight, sex, drug material, and race have a limited effect on drug exposure and do not require any dose adjustment. A typical 50% decrease in linear CL from initial treatment to steady\u2010state was predicted, and this decrease correlated with the best overall response rate and was slower for patients with IgG MM. These findings suggest that the time\u2010dependent effect of isatuximab is likely mediated by a combined factor of both disease state evolution and the perturbation of the FcRn\u2010mediated recycling pathway.<\/jats:p>","DOI":"10.1002\/psp4.12561","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T03:30:08Z","timestamp":1601955008000},"page":"649-658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Drug\u2010Disease Interaction and Time\u2010Dependent Population Pharmacokinetics of Isatuximab in Relapsed\/Refractory Multiple Myeloma Patients"],"prefix":"10.1002","volume":"9","author":[{"given":"Jean\u2010Baptiste","family":"Fau","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":"Claire","family":"Brillac","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiko","family":"Koiwai","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Mace","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Campana","sequence":"additional","affiliation":[{"name":"Sanofi Oncology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Semiond","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine and Early Development Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Sanofi Translational Medicine &amp; Early Development Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0695"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.240"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12389"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1217374"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-02-895193"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32556-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.4065\/78.1.21"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199683307.001.0001"},{"key":"e_1_2_11_10_1","unstructured":"US Food and Drug Administration. 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