{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:58:32Z","timestamp":1787068712295,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"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":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Polatuzumab vedotin is a CD79b\u2010directed antibody\u2013drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R\u2010CHP) as first\u2010line treatment of diffuse large B\u2010cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using a previously developed popPK model, and exposure\u2013response (ER) analysis, were performed. The popPK analysis showed no clinically meaningful relationship between cycle 6 (C6) antibody\u2010conjugated (acMMAE)\/unconjugated MMAE area under the concentration\u2013time curve (AUC) or maximum concentration, and weight, sex, ethnicity, region, mild or moderate renal impairment, mild hepatic impairment, or other patient and disease characteristics. In the ER analysis, C6 acMMAE AUC was significantly associated with longer progression\u2010free and event\u2010free survival (both\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01). An increase of &lt;50% in acMMAE\/unconjugated MMAE exposure did not lead to a clinically meaningful increase in adverse events of special interest. ER data and the benefit\u2013risk profile support the use of polatuzumab vedotin 1.8\u2009mg\/kg once every 3\u2009weeks with R\u2010CHP for six cycles in patients with previously untreated DLBCL.\n                  <\/jats:p>","DOI":"10.1002\/psp4.13141","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T01:40:36Z","timestamp":1713231636000},"page":"1055-1066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Population pharmacokinetics and exposure\u2013response analyses of polatuzumab vedotin in patients with previously untreated\n                    <scp>DLBCL<\/scp>\n                    from the\n                    <scp>POLARIX<\/scp>\n                    study"],"prefix":"10.1002","volume":"13","author":[{"given":"Rong","family":"Deng","sequence":"first","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-7760","authenticated-orcid":false,"given":"Leonid","family":"Gibiansky","sequence":"additional","affiliation":[{"name":"QuantPharm LLC  North Potomac Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-6857","authenticated-orcid":false,"given":"Tong","family":"Lu","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Flowers","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie H.","family":"Sehn","sequence":"additional","affiliation":[{"name":"BC Cancer Centre for Lymphoid Cancer and The University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Z.","family":"Liao","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Dere","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Lee","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Man","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Hirata","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunze","family":"Li","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6351-0441","authenticated-orcid":false,"given":"Dale","family":"Miles","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.15.163998"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2027612"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-205500"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.48"},{"key":"e_1_2_11_6_1","unstructured":"Chugai Pharmaceutical Co. Ltd.Chugai Obtains Regulatory Approval for POLIVY for Additional Indication of Previously Untreated Diffuse Large B\u2010cell Lymphoma.https:\/\/www.chugai\u2010pharm.co.jp\/english\/news\/detail\/20220824150000_944.html. Accessed February 26 2024."},{"key":"e_1_2_11_7_1","unstructured":"ClinicalTrials.gov.A Phase III multicenter randomized double\u2010blind placebo\u2010controlled trial comparing the efficacy and safety of polatuzumab vedotin in combination with rituximab and CHP (R\u2010CHP) versus rituximab and CHOP (R\u2010CHOP) in previously untreated patients with diffuse large B\u2010cell lymphoma.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03274492. Accessed February 26 2024."},{"key":"e_1_2_11_8_1","unstructured":"POLIVY\u00ae Summary of Product Characteristics.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/polivy\u2010epar\u2010product\u2010information_en.pdf. Accessed February 29 2024."},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2115304"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.2530"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12015"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-020-04054-8"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1795154"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12482"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13074"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1682"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2019.1699768"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2016.1156829"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14662"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1953"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.628"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0415"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.13141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T16:13:06Z","timestamp":1718467986000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.13141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,15]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/psp4.13141"],"URL":"https:\/\/doi.org\/10.1002\/psp4.13141","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,15]]},"assertion":[{"value":"2024-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}