{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:23:55Z","timestamp":1790634235317,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study evaluated venetoclax population pharmacokinetics (popPK) in patients with treatment\u2010na\u00efve acute myeloid leukemia and assessed the relationship between venetoclax exposure and clinical response for venetoclax in combination with either a hypomethylating agent (HMA) or low\u2010dose cytarabine (LDAC). A total of 771 patients who received venetoclax from 5 Phase 1\u20133 studies were included in the popPK model. Exposure\u2010response analyses included data from 575 patients for venetoclax\/placebo plus HMA and 279 patients for venetoclax\/placebo plus LDAC. The popPK model successfully characterized venetoclax plasma concentrations over time and confirmed venetoclax exposure did not vary significantly with age, weight, sex, mild to moderate hepatic impairment, or mild to severe renal impairment. Asian patients had 67% higher mean relative bioavailability than non\u2010Asian patients, however the range of exposures in Asian patients was similar to non\u2010Asian patients. For all efficacy endpoints with both treatment combinations, efficacy was higher in the venetoclax treatment groups compared with the respective control arm of placebo plus azacitidine or LDAC. Within patients who received venetoclax, no significant exposure\u2010efficacy relationships were identified for either treatment combination, indicating that the beneficial effects of venetoclax were already maximized in the dose ranges studied. There was no apparent effect of venetoclax exposure on treatment\u2010emergent Grade \u22653 thrombocytopenia or infections for either combination. Rates of treatment\u2010emergent Grade \u22653 neutropenia were higher in the venetoclax treatment arms compared with the respective control arms; however, within patients who received venetoclax, there was only a shallow relationship or no apparent relationship with venetoclax exposure for venetoclax plus HMA or LDAC, respectively. Along with the efficacy and safety data previously published, the exposure\u2010response analyses support the venetoclax dose regimens of 400\u00a0mg once daily (QD) plus HMA and 600\u00a0mg QD plus LDAC in treatment\u2010na\u00efve AML patients who are ineligible for intensive chemotherapy.<\/jats:p>","DOI":"10.1002\/hon.2964","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T08:14:12Z","timestamp":1642580052000},"page":"269-279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Venetoclax exposure\u2010efficacy and exposure\u2010safety relationships in patients with treatment\u2010na\u00efve acute myeloid leukemia who are ineligible for intensive chemotherapy"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-4554","authenticated-orcid":false,"given":"Deanna","family":"Brackman","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doerthe","family":"Eckert","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH Co. KG  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Menon","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-1583","authenticated-orcid":false,"given":"Ahmed Hamed","family":"Salem","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalaja","family":"Potluri","sequence":"additional","affiliation":[{"name":"Oncology Development AbbVie Inc.  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South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Mensing","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH Co. KG  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathej","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH Co. KG  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuhong","family":"Zha","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Inc.  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