{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T14:54:21Z","timestamp":1785596061496,"version":"3.56.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"Genetech Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1007\/s12325-022-02170-w","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T12:12:54Z","timestamp":1655381574000},"page":"3635-3653","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacokinetics and Exposure-Response Analysis of Venetoclax\u2009+\u2009Obinutuzumab in Chronic Lymphocytic Leukemia: Phase\u00a01b Study and Phase\u00a03 CLL14 Trial"],"prefix":"10.1007","volume":"39","clinical-trial-number":[{"clinical-trial-number":"nct02242942","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02339181","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-2044","authenticated-orcid":false,"given":"Divya","family":"Samineni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Gibiansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Vadhavkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Rajwanshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maneesh","family":"Tandon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arijit","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Othman","family":"Al-Sawaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Hamed","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunze","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Miles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"2170_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.annonc.2020.09.019","volume":"32","author":"B Eichhorst","year":"2020","unstructured":"Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines. Ann Oncol. 2020;32:23\u201333.","journal-title":"Ann Oncol"},{"key":"2170_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21387","volume":"67","author":"RL Siegel","year":"2017","unstructured":"Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7\u201330.","journal-title":"CA Cancer J Clin"},{"key":"2170_CR3","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/ajh.24826","volume":"92","author":"M Hallek","year":"2017","unstructured":"Hallek M. Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2017;92:946\u201365.","journal-title":"Am J Hematol"},{"key":"2170_CR4","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s40262-016-0453-9","volume":"56","author":"KJ Freise","year":"2017","unstructured":"Freise KJ, Jones AK, Eckert D, et al. Impact of venetoclax exposure on clinical efficacy and safety inpatients with relapsed or refractory chronic lymphocytic leukemia. Clin Pharmacokinet. 2017;56:515\u201323.","journal-title":"Clin Pharmacokinet"},{"key":"2170_CR5","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1080\/10428194.2017.1361024","volume":"59","author":"A Parikh","year":"2018","unstructured":"Parikh A, Gopalakrishnan S, Freise KJ, et al. Exposure\u2013response evaluations of venetoclax efficacy and safety in patients with non-Hodgkin lymphoma. Leuk Lymphoma. 2018;59:871\u20139.","journal-title":"Leuk Lymphoma"},{"key":"2170_CR6","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1200\/JCO.2016.70.4320","volume":"35","author":"MS Davids","year":"2017","unstructured":"Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35:826\u201333.","journal-title":"J Clin Oncol"},{"key":"2170_CR7","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1056\/NEJMoa1713976","volume":"378","author":"JF Seymour","year":"2018","unstructured":"Seymour JF, Kipps TJ, Eichhorst E, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378:1107\u201320.","journal-title":"N Engl J Med"},{"key":"2170_CR8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1080\/10428194.2019.1657575","volume":"61","author":"R Deng","year":"2020","unstructured":"Deng R, Gibianksy L, Lu T, et al. Exposure-response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: pooled results from a phase\u00a01b study and the phase\u00a03 MURANO study. Leuk Lymph. 2020;61:56\u201365.","journal-title":"Leuk Lymph"},{"key":"2170_CR9","unstructured":"VENCLEXTA\u2122: highlights of prescribing information. VENCLEXTA\u2122 (venetoclax) tablets, for oral use. Initial US Approval: 2016. Revised: June 2018. North Chicago, IL, USA: AbbVie Inc."},{"key":"2170_CR10","doi-asserted-by":"publisher","first-page":"4393","DOI":"10.1182\/blood-2009-06-225979","volume":"115","author":"E M\u00f6ssner","year":"2010","unstructured":"M\u00f6ssner E, Brunker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type of anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115:4393\u2013402.","journal-title":"Blood"},{"key":"2170_CR11","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1365-2141.2010.08428.x","volume":"152","author":"M Patz","year":"2010","unstructured":"Patz M, Isaeva P, Forcob N, et al. Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells. Br J Haematol. 2010;152:295\u2013306.","journal-title":"Br J Haematol"},{"key":"2170_CR12","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1056\/NEJMoa1313984","volume":"370","author":"V Goede","year":"2014","unstructured":"Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370:1101\u201310.","journal-title":"N Engl J Med"},{"issue":"S1","key":"2170_CR13","first-page":"30","volume":"2","author":"V Goede","year":"2018","unstructured":"Goede V, Fischer K, Dyer MJS, et al. Overall survival benefit of obinutuzumab over rituximab when combined with chlorambucil in patients with chronic lymphoytic leukemia and comorbidities: final survival analysis of the CLL11 study [EHA 2018 Abstract S151]. HemaSphere. 2018;2(S1):30.","journal-title":"HemaSphere"},{"key":"2170_CR14","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1056\/NEJMoa1815281","volume":"380","author":"K Fischer","year":"2019","unstructured":"Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225\u201336.","journal-title":"N Engl J Med"},{"key":"2170_CR15","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/S1470-2045(20)30443-5","volume":"21","author":"O Al-Sawaf","year":"2020","unstructured":"Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase\u00a03 trial. Lancet Oncol. 2020;21:1188\u2013200.","journal-title":"Lancet Oncol"},{"issue":"S1","key":"2170_CR16","first-page":"30","volume":"4","author":"O Al-Sawaf","year":"2020","unstructured":"Al-Sawaf O, Zhang C, Tandon M, et al. Fixed-duration venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: follow-up of efficacy and safety results from the multicenter, open-label, randomised phase\u00a03 CLL14 trial [EHA 2020 Abstract S155]. HemaSphere. 2020;4(S1):30.","journal-title":"HemaSphere"},{"key":"2170_CR17","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1182\/blood-2019-01-896290","volume":"133","author":"IW Flinn","year":"2019","unstructured":"Flinn IW, Gribben JG, Dyer MJS, et al. Phase\u00a01b study of venetoclax-obinutuzumab in previously untreated and relapsed\/refractory chronic lymphocytic leukemia. Blood. 2019;133:2765\u201375.","journal-title":"Blood"},{"key":"2170_CR18","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s40261-016-0485-9","volume":"37","author":"AH Salem","year":"2017","unstructured":"Salem AH, Hu B, Freise KJ, et al. Evaluation of the pharmacokinetic interaction between venetoclax, a selective BCL-2 inhibitor, and warfarin in healthy volunteers. Clin Drug Investig. 2017;37:303\u20139.","journal-title":"Clin Drug Investig"},{"key":"2170_CR19","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1124\/dmd.116.071613","volume":"45","author":"H Liu","year":"2017","unstructured":"Liu H, Michmerhuizen MJ, Lao Y, Wan K, et al. Metabolism and disposition of a novel B-cell lymphoma-2 inhibitor venetoclax in humans and characterisation of its unusual metabolites. Drug Metab Dispos. 2017;45:294\u2013305.","journal-title":"Drug Metab Dispos"},{"key":"2170_CR20","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1208\/s12248-016-9927-9","volume":"18","author":"AK Jones","year":"2016","unstructured":"Jones AK, Freise KJ, Agarwal SK, Humerickhouse RA, Wong SL, Salem AH. Clinical predictors of venetoclax pharmacokinetics in chronic lymphocytic leukemia and non-Hodgkin\u2019s lymphoma patients: a pooled population pharmacokinetic analysis. AAPS J. 2016;18:1192\u2013202.","journal-title":"AAPS J"},{"key":"2170_CR21","volume-title":"NONMEM user\u2019s guides (1989\u20132011)","author":"S Beal","year":"2011","unstructured":"Beal S, Sheiner LB, Boeckmann A, Bauer RJ. NONMEM user\u2019s guides (1989\u20132011). Ellicott City: Icon Development Solutions; 2011."},{"key":"2170_CR22","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S1470-2045(16)30019-5","volume":"17","author":"S Stilgenbauer","year":"2016","unstructured":"Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukemia with 17p deletion: a multicenter, open-label phase 2 study. Lancet Oncol. 2016;17:768\u201378.","journal-title":"Lancet Oncol"},{"key":"2170_CR23","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1097\/CAD.0000000000000522","volume":"28","author":"AH Salem","year":"2017","unstructured":"Salem AH, Dunbar M, Agarwal SK. Pharmacokinetics of venetoclax in patients with 17p deletion chronic lymphocytic leukemia. Anticancer Drugs. 2017;28:911\u20134.","journal-title":"Anticancer Drugs"},{"key":"2170_CR24","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1007\/s40262-019-00788-8","volume":"58","author":"R Deng","year":"2019","unstructured":"Deng R, Gibianksy L, Lu T, et al. Bayesian population model of the pharmacokinetics of venetoclax in combination with rituximab in patients with relapsed\/refractory chronic lymphocytic leukemia: results from the phase III MURANO study. Clin Pharmacokinet. 2019;58:1621\u201334.","journal-title":"Clin Pharmacokinet"},{"key":"2170_CR25","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1111\/bcp.13175","volume":"83","author":"SK Agarwal","year":"2017","unstructured":"Agarwal SK, Salem AH, Danilov AV, et al. Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL-2 inhibitor, in patients with non-Hodgkin lymphoma. Br J Clin Pharmacol. 2017;83:846\u201354.","journal-title":"Br J Clin Pharmacol"},{"key":"2170_CR26","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1002\/jcph.858","volume":"57","author":"KJ Freise","year":"2017","unstructured":"Freise KJ, Shebley M, Salem AH. Quantitative prediction of the effect of CYP3A inhibitors and inducers on venetoclax pharmacokinetics using a physiologically based pharmacokinetic model. J Clin Pharmacol. 2017;57:796\u2013804.","journal-title":"J Clin Pharmacol"},{"key":"2170_CR27","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00228-017-2403-3","volume":"74","author":"KJ Freise","year":"2018","unstructured":"Freise KJ, Hu B, Salem AH. Impact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics. Eur J Clin Pharmacol. 2018;74:413\u201321.","journal-title":"Eur J Clin Pharmacol"},{"key":"2170_CR28","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.clinthera.2017.01.003","volume":"39","author":"SK Agarwal","year":"2017","unstructured":"Agarwal SK, DiNardo CD, Potluri J, et al. Management of venetoclax-posaconazole interaction in acuter myeloid leukemia patients: evaluation of dose adjustments. Clin Ther. 2017;39:359\u201367.","journal-title":"Clin Ther"}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-022-02170-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12325-022-02170-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-022-02170-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T18:14:32Z","timestamp":1658686472000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12325-022-02170-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,16]]},"references-count":28,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["2170"],"URL":"https:\/\/doi.org\/10.1007\/s12325-022-02170-w","relation":{},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,16]]},"assertion":[{"value":"3 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}