{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:39:46Z","timestamp":1773977986539,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T00:00:00Z","timestamp":1695427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Venetoclax, a potent BCL\u20102 inhibitor, is currently under development for treatment of t(11;14) Multiple myeloma (MM). The objective of this research was to investigate the exposure\u2013response relationships of venetoclax for a phase 1\/2 study evaluating venetoclax monotherapy or in combination with dexamethasone in relapsed or refractory MM. A total of 117 patients receiving venetoclax at 300, 600, 800, 900, or 1200\u00a0mg were included in the analysis. The impact of venetoclax exposures on efficacy (objective response rate [ORR], progression\u2010free survival [PFS] and overall survival [OS]) as well as safety (treatment\u2010emergent adverse effects (grade \u22653) of neutropenia, infection, and any grade of serious treatment\u2010emergent adverse effects) was evaluated. In the t(11;14)\u2010positive subpopulation, venetoclax exposure relationships to PFS and OS indicated a trend of longer PFS and OS with higher exposures. Moreover, logistic regression analyses for clinical response (ORR and \u2265VGPR rate) demonstrated a statistically significant (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05) relationship with exposure. Evaluation of the exposure\u2010safety relationships demonstrated a lack of a relationship between venetoclax exposures (AUC\n                    <jats:sub>avg<\/jats:sub>\n                    ) and grade \u22653 infections, grade \u22653 neutropenia, grade \u22653 treatment\u2010emergent adverse events or any grade serious treatment\u2010emergent adverse events. These findings support further study of venetoclax at 800\u00a0mg QD dose in combination with dexamethasone in the t(11;14)\u2010positive patient population where increased efficacy was observed without an increase in safety events.Clinical Trial: NCT01794520 registered 20 February 2013.\n                  <\/jats:p>","DOI":"10.1002\/hon.3222","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T13:49:14Z","timestamp":1695476954000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Venetoclax in biomarker\u2010selected multiple myeloma patients: Impact of exposure on clinical efficacy and safety"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9033-2436","authenticated-orcid":false,"given":"Mohamed","family":"Badawi","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie, Inc  North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-5962","authenticated-orcid":false,"given":"Sheryl","family":"Coppola","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie, Inc  North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doerthe","family":"Eckert","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0923-034X","authenticated-orcid":false,"given":"Sathej","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Doelger","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weize","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Genentech Inc  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edyta","family":"Dobkowska","sequence":"additional","affiliation":[{"name":"Clinical Development Pharmacyclics Switzerland GmbH An AbbVie Company  Schaffhausen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaji","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-0449","authenticated-orcid":false,"given":"Rajeev M.","family":"Menon","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie, Inc  North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-1583","authenticated-orcid":false,"given":"Ahmed Hamed","family":"Salem","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201005\u2010743203"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24236"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201010\u2010116129"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201008\u2010104984"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31937"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11060463"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001482"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201020\u20104842"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201017\u20100797"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.216"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.350"},{"key":"e_1_2_13_13_1","unstructured":"AbbVie Inc.Study evaluating ABT\u2010199 in participants with relapsed or refractory multiple myeloma. ClinicalTrials.gov identifier: NCT01794520 (M13\u2010367. Last updated April 8 2021. Accessed 4 May 2021.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01794520"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201006\u2010788786"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.071613"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010016\u20109927\u20109"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2964"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010021\u201001919\u2010z"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010016\u20100453\u20109"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1657575"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010022\u201002170\u2010w"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2373"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2017.1361024"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201015\u20100730"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.553"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00443"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020004146"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102022\u2010166429"}],"container-title":["Hematological Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.3222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:10:00Z","timestamp":1711451400000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hon.3222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,23]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/hon.3222"],"URL":"https:\/\/doi.org\/10.1002\/hon.3222","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/HON.3222\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.3222\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.3222\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0278-0232","1099-1069"],"issn-type":[{"value":"0278-0232","type":"print"},{"value":"1099-1069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,23]]},"assertion":[{"value":"2023-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3222"}}