{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:26:10Z","timestamp":1791563170047,"version":"4.3.4"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100014561","name":"Juno Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014561","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1007\/s40262-021-01039-5","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T06:02:26Z","timestamp":1623650546000},"page":"1621-1633","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Population Cellular Kinetics of Lisocabtagene Maraleucel, an Autologous CD19-Directed Chimeric Antigen Receptor T-Cell Product, in Patients with Relapsed\/Refractory Large B-Cell Lymphoma"],"prefix":"10.1007","volume":"60","clinical-trial-number":[{"clinical-trial-number":"nct02631044","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4264-8927","authenticated-orcid":false,"given":"Ken","family":"Ogasawara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dodds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Mack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Lymp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Dell\u2019Aringa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"issue":"10254","key":"1039_CR1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","volume":"396","author":"JS Abramson","year":"2020","unstructured":"Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839\u201352.","journal-title":"Lancet"},{"issue":"Suppl 1","key":"1039_CR2","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1182\/blood-2019-127150","volume":"134","author":"J Teoh","year":"2019","unstructured":"Teoh J, Johnstone T, Christin B, Yost R, Haig N, Mallaney M, et al. Lisocabtagene maraleucel (liso-cel) manufacturing process control and robustness across CD19+ hematological malignancies [abstract]. Blood. 2019;134(Suppl 1):593.","journal-title":"Blood"},{"key":"1039_CR3","doi-asserted-by":"crossref","unstructured":"Turtle CJ, Hanafi LA, Berger C, Hudecek M, Pender B, Robinson E, et al. Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8(355):355ra116.","DOI":"10.1126\/scitranslmed.aaf8621"},{"issue":"11","key":"1039_CR4","doi-asserted-by":"publisher","first-page":"4262","DOI":"10.1172\/JCI84813","volume":"126","author":"PJ Paszkiewicz","year":"2016","unstructured":"Paszkiewicz PJ, Fr\u00e4\u00dfle SP, Srivastava S, Sommermeyer D, Hudecek M, Drexler I, et al. Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia. J Clin Invest. 2016;126(11):4262\u201372.","journal-title":"J Clin Invest"},{"issue":"5","key":"1039_CR5","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1182\/blood-2011-02-337360","volume":"118","author":"X Wang","year":"2011","unstructured":"Wang X, Chang WC, Wong CW, Colcher D, Sherman M, Ostberg JR, et al. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood. 2011;118(5):1255\u201363.","journal-title":"Blood"},{"issue":"5","key":"1039_CR6","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1634\/theoncologist.2015-0421","volume":"21","author":"MV Maus","year":"2016","unstructured":"Maus MV, Levine BL. Chimeric antigen receptor T-cell therapy for the community oncologist. Oncologist. 2016;21(5):608\u201317.","journal-title":"Oncologist"},{"issue":"16","key":"1039_CR7","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1200\/JCO.2016.71.3024","volume":"35","author":"JN Kochenderfer","year":"2017","unstructured":"Kochenderfer JN, Somerville RPT, Lu T, Shi V, Bot A, Rossi J, et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J Clin Oncol. 2017;35(16):1803\u201313.","journal-title":"J Clin Oncol"},{"issue":"26","key":"1039_CR8","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","volume":"377","author":"SS Neelapu","year":"2017","unstructured":"Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531\u201344.","journal-title":"N Engl J Med"},{"issue":"1","key":"1039_CR9","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1056\/NEJMoa1804980","volume":"380","author":"SJ Schuster","year":"2019","unstructured":"Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45\u201356.","journal-title":"N Engl J Med"},{"issue":"5","key":"1039_CR10","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/psp4.12388","volume":"8","author":"AM Stein","year":"2019","unstructured":"Stein AM, Grupp SA, Levine JE, Laetsch TW, Pulsipher MA, Boyer MW, et al. Tisagenlecleucel model-based cellular kinetic analysis of chimeric antigen receptor-T cells. CPT Pharmacometrics Syst Pharmacol. 2019;8(5):285\u201395.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"21","key":"1039_CR11","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1182\/blood-2017-06-786129","volume":"130","author":"KT Mueller","year":"2017","unstructured":"Mueller KT, Maude SL, Porter DL, Frey N, Wood P, Han X, et al. Cellular kinetics of CTL019 in relapsed\/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia. Blood. 2017;130(21):2317\u201325.","journal-title":"Blood"},{"issue":"24","key":"1039_CR12","doi-asserted-by":"publisher","first-page":"6175","DOI":"10.1158\/1078-0432.CCR-18-0758","volume":"24","author":"KT Mueller","year":"2018","unstructured":"Mueller KT, Waldron E, Grupp SA, Levine JE, Laetsch TW, Pulsipher MA, et al. Clinical pharmacology of tisagenlecleucel in B-cell acute lymphoblastic leukemia. Clin Cancer Res. 2018;24(24):6175\u201384.","journal-title":"Clin Cancer Res"},{"issue":"3","key":"1039_CR13","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1182\/bloodadvances.2019000525","volume":"4","author":"R Awasthi","year":"2020","unstructured":"Awasthi R, Pacaud L, Waldron E, Tam CS, J\u00e4ger U, Borchmann P, et al. Tisagenlecleucel cellular kinetics, dose, and immunogenicity in relation to clinical factors in relapsed\/refractory DLBCL. Blood Adv. 2020;4(3):560\u201372.","journal-title":"Blood Adv"},{"key":"1039_CR14","unstructured":"YESCARTA (axicbatagene ciloleucel) [summary of product characteristics]. Amsterdam, The Netherlands: Kite Pharma EU B.V.; 2018."},{"key":"1039_CR15","unstructured":"KYMRIAH (tisagenlecleucel) [summary of product characteristics]. Dublin: Novartis Europharm Limited; 2018."},{"issue":"3","key":"1039_CR16","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.cmpb.2005.04.005","volume":"79","author":"L Lindbom","year":"2005","unstructured":"Lindbom L, Pihlgren P, Jonsson EN. PsN-Toolkit\u2014a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed. 2005;79(3):241\u201357.","journal-title":"Comput Methods Programs Biomed"},{"key":"1039_CR17","unstructured":"Bauer R. NONMEM Users Guide. Introduction to NONMEM 7.4.1. 2017. https:\/\/nonmem.iconplc.com\/nonmem741. Accessed 30 Apr 2020."},{"key":"1039_CR18","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jtbi.2012.12.025","volume":"327","author":"RJ De Boer","year":"2013","unstructured":"De Boer RJ, Perelson AS. Quantifying T lymphocyte turnover. J Theor Biol. 2013;327:45\u201387.","journal-title":"J Theor Biol"},{"key":"1039_CR19","unstructured":"US Food and Drug Administration. Pharmacometric review of axicabtagene ciloleucel. 2017. https:\/\/www.fda.gov\/media\/109140\/download. Accessed 5 May 2020."},{"issue":"3","key":"1039_CR20","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1208\/s12248-009-9133-0","volume":"11","author":"RM Savic","year":"2009","unstructured":"Savic RM, Karlsson MO. Importance of shrinkage in empirical Bayes estimates for diagnostics: problems and solutions. AAPS J. 2009;11(3):558\u201369.","journal-title":"AAPS J"},{"key":"1039_CR21","volume-title":"Brock biology of microorganisms","author":"M Madigan","year":"1997","unstructured":"Madigan M, Martinko J, Parker J. Brock biology of microorganisms. 8th ed. London: Prentice Hall, Inc.; 1997.","edition":"8"},{"issue":"3","key":"1039_CR22","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1124\/jpet.118.252858","volume":"368","author":"A Khot","year":"2019","unstructured":"Khot A, Matsueda S, Thomas VA, Koya RC, Shah DK. Measurement and quantitative characterization of whole-body pharmacokinetics of exogenously administered T cells in mice. J Pharmacol Exp Ther. 2019;368(3):503\u201313.","journal-title":"J Pharmacol Exp Ther"},{"key":"1039_CR23","unstructured":"BREYANZI (lisocabtagene maraleucel) [prescribing information]. Princeton, NJ: Bristol Myers Squibb; 2021."},{"key":"1039_CR24","doi-asserted-by":"crossref","unstructured":"Zwietering MH, Jongenburger I, Rombouts FM, van 't Riet K. Modeling of the bacterial growth curve. Appl Environ Microbiol. 1990;56(6):1875\u201381.","DOI":"10.1128\/aem.56.6.1875-1881.1990"},{"key":"1039_CR25","doi-asserted-by":"crossref","unstructured":"Salter AI, Ivey RG, Kennedy JJ, Voillet V, Rajan A, Alderman EJ, et al. Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function. Sci Signal. 2018;11(544):eaat6753.","DOI":"10.1126\/scisignal.aat6753"},{"issue":"2","key":"1039_CR26","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.jgo.2020.08.004","volume":"12","author":"JL Jaggers","year":"2021","unstructured":"Jaggers JL, Giri S, Klepin HD, Wildes TM, Olin RL, Artz A, et al. Characterizing inclusion and exclusion criteria in clinical trials for chimeric antigen receptor (CAR) T-cell therapy among adults with hematologic malignancies. J Geriatr Oncol. 2021;12(2):235\u20138.","journal-title":"J Geriatr Oncol."}],"updated-by":[{"DOI":"10.1007\/s40262-021-01055-5","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T00:00:00Z","timestamp":1625270400000}}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-021-01039-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-021-01039-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-021-01039-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T02:05:23Z","timestamp":1637805923000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-021-01039-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,14]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1039"],"URL":"https:\/\/doi.org\/10.1007\/s40262-021-01039-5","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s40262-021-01055-5","asserted-by":"object"}]},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,14]]},"assertion":[{"value":"11 May 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2021","order":3,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":4,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":5,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s40262-021-01055-5","URL":"https:\/\/doi.org\/10.1007\/s40262-021-01055-5","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was funded by Juno Therapeutics, a Bristol-Myers Squibb Company.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Ken Ogasawara, Timothy Mack, James Lymp, Justine Dell\u2019Aringa, and Jeff Smith are employees of Bristol Myers Squibb and hold stock in Bristol Myers Squibb. Michael Dodds is a consultant for Bristol Myers Squibb.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The research was conducted within all the appropriate ethical and legal guidelines.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"For investigations involving human patients, informed consent was obtained from the participants involved.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors approved this manuscript for submission.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Bristol Myers Squibb policy on data sharing may be found at .","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"KO and MD contributed to the study design and data analysis and interpretation. TM, JL, JD, and JS contributed to data acquisition and interpretation. KO drafted the manuscript. All authors critically reviewed the draft manuscript, approved the final version to be published, and agree to be accountable for all aspects of the work.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}