{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:13:17Z","timestamp":1790701997569,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T00:00:00Z","timestamp":1562630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010293","name":"Seattle Genetics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010293","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>\n                    The efficacy of the\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    30\u2010directed antibody\u2010drug conjugate (\n                    <jats:styled-content style=\"fixed-case\">ADC<\/jats:styled-content>\n                    ) brentuximab vedotin was established in combination with chemotherapy as frontline treatment for advanced classical Hodgkin's lymphoma in the randomized phase\n                    <jats:styled-content style=\"fixed-case\">III ECHELON<\/jats:styled-content>\n                    \u20101 study. Population pharmacokinetic (\n                    <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\n                    ) and exposure\u2013response models were developed to quantify sources of\n                    <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\n                    variability and relationships between exposure and safety\/efficacy end points in\n                    <jats:styled-content style=\"fixed-case\">ECHELON<\/jats:styled-content>\n                    \u20101. The influence of patient\u2010specific factors on the\n                    <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\n                    of the\n                    <jats:styled-content style=\"fixed-case\">ADC<\/jats:styled-content>\n                    and the microtubule\u2010disrupting payload monomethyl auristatin E (\n                    <jats:styled-content style=\"fixed-case\">MMAE<\/jats:styled-content>\n                    ) was investigated; none of the significant covariates had a clinically relevant impact. Exposure\u2013response analyses evaluated relationships between time\u2010averaged area under the curve (\n                    <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>\n                    ;\n                    <jats:styled-content style=\"fixed-case\">ADC<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">MMAE<\/jats:styled-content>\n                    ) and efficacy end points (\n                    <jats:styled-content style=\"fixed-case\">ADC<\/jats:styled-content>\n                    ) or safety parameters (\n                    <jats:styled-content style=\"fixed-case\">ADC<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">MMAE<\/jats:styled-content>\n                    ). Exposure\u2013efficacy analyses supported consistent treatment benefit with brentuximab vedotin across observed exposure ranges. Exposure\u2010safety analyses supported the recommended brentuximab vedotin starting dose (1.2\u00a0mg\/kg every 2\u00a0weeks), and effective management of peripheral neuropathy and neutropenia with dose modification\/reduction and febrile neutropenia with granulocyte colony\u2010stimulating factor primary prophylaxis.\n                  <\/jats:p>","DOI":"10.1002\/cpt.1530","type":"journal-article","created":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T10:16:05Z","timestamp":1559384165000},"page":"1268-1279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Population Pharmacokinetic Modeling and Exposure\u2013Response Assessment for the Antibody\u2010Drug Conjugate Brentuximab Vedotin in Hodgkin's Lymphoma in the Phase III ECHELON\u20101 Study"],"prefix":"10.1111","volume":"106","author":[{"given":"Ajit","family":"Suri","sequence":"first","affiliation":[{"name":"Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane R.","family":"Mould","sequence":"additional","affiliation":[{"name":"Projections Research, Inc.  Phoenixville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Song","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham P.","family":"Collins","sequence":"additional","affiliation":[{"name":"Oxford Cancer and Haematology Centre Oxford University Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Endres","sequence":"additional","affiliation":[{"name":"Seattle Genetics, Inc.  Bothell Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Gomez\u2010Navarro","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2016.11.009"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000168"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2017.85"},{"key":"e_1_2_11_4_1","unstructured":"Seattle Genetics.ADCETRIS\u00ae(brentuximab vedotin). [prescribing information]. <https:\/\/www.adcetris.com\/presinfo\/pi.pdf> (November2018). Accessed December 5 2018."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.0410"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-699850"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60165-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31266-7"},{"key":"e_1_2_11_9_1","unstructured":"Takeda Pharma A\/S.ADCETRIS\u00ae(brentuximab vedotin). Summary of product characteristics<https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/adcetris#product-information-section> (2019). Accessed March 28 2019."},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70501-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708984"},{"key":"e_1_2_11_12_1","unstructured":"Takeda Pharmaceutical Company Limited.Takeda obtains additional indication and dosage & administration for ADCETRIS\u00aeas a frontline treatment for CD30\u2010positive Hodgkin Lymphoma in Japan<https:\/\/www.takeda.com\/newsroom\/newsreleases\/2018\/takeda-obtains-additional-indication-and-dosage-administration-for-adcetris-asa-frontline-treatment-for-cd30-positive-hodgkin-lymphoma-in-japan\/;> (2018). 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