{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:53:04Z","timestamp":1791240784310,"version":"4.1.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2016,5,21]],"date-time":"2016-05-21T00:00:00Z","timestamp":1463788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1007\/s40262-016-0405-4","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T01:20:13Z","timestamp":1464052813000},"page":"1271-1288","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":206,"title":["Blinatumomab, a Bispecific T-cell Engager (BiTE\u00ae) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications"],"prefix":"10.1007","volume":"55","author":[{"given":"Min","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Brandl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Doshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,21]]},"reference":[{"key":"405_CR1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1126\/science.1158545","volume":"321","author":"R Bargou","year":"2008","unstructured":"Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008;321:974\u20137.","journal-title":"Science"},{"key":"405_CR2","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1080\/10428190902943077","volume":"50","author":"D Nagorsen","year":"2009","unstructured":"Nagorsen D, Bargou R, Ruttinger D, Kufer P, Baeuerle PA, Zugmaier G. Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leuk Lymphoma. 2009;50:886\u201391.","journal-title":"Leuk Lymphoma"},{"key":"405_CR3","unstructured":"Blincyto\u2122 (blinatumomab) prescribing information. Thousand Oaks, CA, USA: Amgen Inc.; 2014."},{"key":"405_CR4","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1158\/1078-0432.CCR-15-0612","volume":"21","author":"D Przepiorka","year":"2015","unstructured":"Przepiorka D, Ko C-W, Deisseroth A, Yancey CL, Candau-Chacon R, Chiu H-J, et al. FDA approval: blinatumomab. Clin Cancer Res. 2015;21:4035\u20139.","journal-title":"Clin Cancer Res."},{"key":"405_CR5","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.1182\/blood-2012-01-400515","volume":"119","author":"M Klinger","year":"2012","unstructured":"Klinger M, Brandl C, Zugmaier G, Hijazi Y, Bargou RC, Topp MS, et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19\/CD3-bispecific BiTE antibody blinatumomab. Blood. 2012;119:6226\u201333.","journal-title":"Blood"},{"key":"405_CR6","doi-asserted-by":"crossref","unstructured":"Hijazi Y, Klinger M, Schub A, Wu B, Zhu M, Kufer P, et al. Blinatumomab exposure and pharmacodynamic response in patients with non-Hodgkin lymphoma (NHL). J Clin Oncol. 2013;31(15 suppl):Abstract 3051.","DOI":"10.1200\/jco.2013.31.15_suppl.3051"},{"key":"405_CR7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/intimm\/dxu089","volume":"27","author":"Z Zimmerman","year":"2015","unstructured":"Zimmerman Z, Maniar T, Nagorsen D. Unleashing the clinical power of T cells: CD19\/CD3 bi-specific T cell engager (BiTE\u00ae) antibody construct blinatumomab as a potential therapy. Int Immunol. 2015;27:31\u20137.","journal-title":"Int Immunol"},{"key":"405_CR8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S1470-2045(14)71170-2","volume":"16","author":"MS Topp","year":"2015","unstructured":"Topp MS, G\u00f6kbuget N, Stein AS, Zugmaier G, O\u2019Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16:57\u201366.","journal-title":"Lancet Oncol."},{"key":"405_CR9","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/icb.2014.93","volume":"93","author":"AM Huehls","year":"2015","unstructured":"Huehls AM, Coupet TA, Sentman CL. Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol. 2015;93:290\u20136.","journal-title":"Immunol Cell Biol"},{"key":"405_CR10","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.3109\/10428194.2011.559668","volume":"52","author":"S Raponi","year":"2011","unstructured":"Raponi S, De Propris MS, Intoppa S, Milani ML, Vitale A, Elia L, et al. Flow cytometric study of potential target antigens (CD19, CD20, CD22, CD33) for antibody-based immunotherapy in acute lymphoblastic leukemia: analysis of 552 cases. Leuk Lymphoma. 2011;52:1098\u2013107.","journal-title":"Leuk Lymphoma"},{"key":"405_CR11","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.yexcr.2011.03.010","volume":"317","author":"D Nagorsen","year":"2011","unstructured":"Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011;317:1255\u201360.","journal-title":"Exp Cell Res"},{"key":"405_CR12","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.imbio.2008.11.014","volume":"214","author":"C Haas","year":"2009","unstructured":"Haas C, Krinner E, Brischwein K, Hoffmann P, Lutterbuse R, Schlereth B, et al. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology. 2009;214:441\u201353.","journal-title":"Immunobiology"},{"key":"405_CR13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.0105-2896.2010.00907.x","volume":"235","author":"DA Anthony","year":"2010","unstructured":"Anthony DA, Andrews DM, Watt SV, Trapani JA, Smyth MJ. Functional dissection of the granzyme family: cell death and inflammation. Immunol Rev. 2010;235:73\u201392.","journal-title":"Immunol Rev"},{"key":"405_CR14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/cdd.2011.153","volume":"19","author":"CL Ewen","year":"2012","unstructured":"Ewen CL, Kane KP, Bleackley RC. A quarter century of granzymes. Cell Death Differ. 2012;19:28\u201335.","journal-title":"Cell Death Differ"},{"key":"405_CR15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.0105-2896.2010.00896.x","volume":"235","author":"I Voskoboinik","year":"2010","unstructured":"Voskoboinik I, Dunstone MA, Baran K, Whisstock JC, Trapani JA. Perforin: structure, function, and role in human immunopathology. Immunol Rev. 2010;235:35\u201354.","journal-title":"Immunol Rev"},{"key":"405_CR16","doi-asserted-by":"crossref","unstructured":"Kontermann RE. Dual targeting strategies with bispecific antibodies. mAbs. 2012;4:182\u2013197.","DOI":"10.4161\/mabs.4.2.19000"},{"key":"405_CR17","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1002\/jcph.445","volume":"55","author":"C Rathi","year":"2015","unstructured":"Rathi C, Meibohm B. Clinical pharmacology of bispecific antibody constructs. J Clin Pharmacol. 2015;55:S21\u20138.","journal-title":"J Clin Pharmacol"},{"key":"405_CR18","first-page":"5","volume":"5","author":"CA Portell","year":"2013","unstructured":"Portell CA, Wenzell CM, Advani AS. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol. 2013;5:5\u201311.","journal-title":"Clin Pharmacol."},{"key":"405_CR19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/jps.23783","volume":"103","author":"B Wu","year":"2014","unstructured":"Wu B, Sun YN. Pharmacokinetics of peptide-Fc fusion proteins. J Pharm Sci. 2014;103:53\u201364.","journal-title":"J Pharm Sci"},{"key":"405_CR20","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1182\/blood-2006-05-018192","volume":"109","author":"AK Fielding","year":"2007","unstructured":"Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12\/ECOG 2993 study. Blood. 2007;109:944\u201350.","journal-title":"Blood"},{"key":"405_CR21","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3324\/haematol.2009.014274","volume":"95","author":"A Oriol","year":"2010","unstructured":"Oriol A, Vives S, Hernandez-Rivas JM, Tormo M, Heras I, Rivas C, et al. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica. 2010;95:589\u201396.","journal-title":"Haematologica"},{"key":"405_CR22","unstructured":"Nagorsen D. Blinatumomab (Blincyto\u2122) indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (Amgen, Inc.). In: Presented at: Accelerating anticancer agent development and validation workshop; May 6\u20138, 2015; Bethesda, MD, USA."},{"key":"405_CR23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1159\/000180580","volume":"16","author":"DW Cockcroft","year":"1976","unstructured":"Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31\u201341.","journal-title":"Nephron."},{"key":"405_CR24","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/psp4.12003","volume":"4","author":"Y Xu","year":"2015","unstructured":"Xu Y, Hijazi Y, Wolf A, Wu B, Sun YN, Zhu M. Physiologically based pharmacokinetic model to assess the influence of blinatumomab-mediated cytokine elevations on cytochrome P450 enzyme activity. CPT Pharmacomet Syst Pharmacol. 2015;4:507\u201315.","journal-title":"CPT Pharmacomet Syst Pharmacol."},{"key":"405_CR25","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/1471-2369-14-246","volume":"14","author":"T Schoen","year":"2013","unstructured":"Schoen T, Blum J, Paccaud F, Burnier M, Bochud M, Conen D, et al. Factors associated with 24-hour urinary volume: the Swiss salt survey. BMC Nephrol. 2013;14:246.","journal-title":"BMC Nephrol."},{"key":"405_CR26","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1002\/jps.20178","volume":"93","author":"ED Lobo","year":"2004","unstructured":"Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93:2645\u201368.","journal-title":"J Pharm Sci"},{"key":"405_CR27","doi-asserted-by":"crossref","unstructured":"Zhu M, Kratzer A, Johnson J, Holland C, Brandl C, Singh I, et al. Pharmacokinetics\/pharmacodynamics (PKPD) of blinatumomab in patients with relapsed\/refractory B-precursor acute lymphoblastic leukemia (r\/r ALL). J Clin Oncol. 2015;33(15 Suppl):Abstract 2561.","DOI":"10.1200\/jco.2015.33.15_suppl.2561"},{"key":"405_CR28","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/clpt.2009.308","volume":"87","author":"SM Huang","year":"2010","unstructured":"Huang SM, Zhao H, Lee JI, Reynolds K, Zhang L, Temple R, et al. Therapeutic protein-drug interactions and implications for drug development. Clin Pharmacol Ther. 2010;87:497\u2013503.","journal-title":"Clin Pharmacol Ther"},{"key":"405_CR29","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.copbio.2006.10.002","volume":"17","author":"AK Sato","year":"2006","unstructured":"Sato AK, Viswanathan M, Kent RB, Wood CR. Therapeutic peptides: technological advances driving peptides into development. Curr Opin Biotechnol. 2006;17:638\u201342.","journal-title":"Curr Opin Biotechnol"},{"key":"405_CR30","unstructured":"Roferon\u00ae (Interferon alfa-2a) prescribing information. Basel, Switzerland: F. Hoffmann-La Roche Ltd.; 2001."},{"key":"405_CR31","unstructured":"Neupogen\u00ae (filgrastim) prescribing information. Thousand Oaks, CA, USA: Amgen; 2015."},{"key":"405_CR32","unstructured":"Cerezyme\u00ae (imiglucerase for injection) prescribing information. Cambridge, MA, USA: Genzyme Corporation; 2011."},{"key":"405_CR33","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s11095-011-0650-z","volume":"29","author":"B Wu","year":"2012","unstructured":"Wu B, Johnson J, Soto M, Ponce M, Calamba D, Sun YN. Investigation of the mechanism of clearance of AMG 386, a selective angiopoietin-1\/2 neutralizing peptibody, in splenectomized, nephrectomized, and FcRn knockout rodent models. Pharm Res. 2012;29:1057\u201365.","journal-title":"Pharm Res"},{"key":"405_CR34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrd2399","volume":"7","author":"B Leader","year":"2008","unstructured":"Leader B, Baca QJ, Golan DE. Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov. 2008;7:21\u201339.","journal-title":"Nat Rev Drug Discov."},{"key":"405_CR35","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/aps.2012.51","volume":"33","author":"L Zhao","year":"2012","unstructured":"Zhao L, Ren TH, Wang DD. Clinical pharmacology considerations in biologics development. Acta Pharmacol Sin. 2012;33:1339\u201347.","journal-title":"Acta Pharmacol Sin"},{"key":"405_CR36","doi-asserted-by":"crossref","first-page":"54S","DOI":"10.1177\/0091270011413894","volume":"52","author":"B Meibohm","year":"2012","unstructured":"Meibohm B, Zhou H. Characterizing the impact of renal impairment on the clinical pharmacology of biologics. J Clin Pharmacol. 2012;52:54S\u201362S.","journal-title":"J Clin Pharmacol"},{"key":"405_CR37","unstructured":"US Food and Drug Administration. Guidance for industry: pharmacokinetics in patients with impaired renal function: study design, data analysis, and impact on dosing and labeling. Draft Guidance. 2010."},{"key":"405_CR38","doi-asserted-by":"crossref","unstructured":"Meijer DKF, Ziegler K. Mechanisms for the hepatic clearance of oligopeptides and proteins: implications for rate of elimination, bioavailability, and cell-specific drug delivery to the liver. In: KL Audus TJRE, editor. Biological barriers to protein delivery. New York: Plenum Press; 1993. p. 339\u2013407.","DOI":"10.1007\/978-1-4615-2898-2_13"},{"key":"405_CR39","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/ijc.20908","volume":"115","author":"P Hoffmann","year":"2005","unstructured":"Hoffmann P, Hofmeister R, Brischwein K, Brandl C, Crommer S, Bargou R, et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-\/CD3-bispecific single-chain antibody construct. Int J Cancer. 2005;115:98\u2013104.","journal-title":"Int J Cancer"},{"key":"405_CR40","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.critrevonc.2014.08.003","volume":"92","author":"R Lameris","year":"2014","unstructured":"Lameris R, de Bruin RC, Schneiders FL, van Bergen en Henegouwen PM, Verheul HM, de Gruijl TD, et al. Bispecific antibody platforms for cancer immunotherapy. Crit Rev Oncol Hematol. 2014;92:153\u201365.","journal-title":"Crit Rev Oncol Hematol"},{"key":"405_CR41","doi-asserted-by":"crossref","unstructured":"Klinger M, Kufer P, Kirchinger P, Lutterbuese P, Leo E, Reinhardt C, et al. T cell responses during long-term continuous infusion of MT103 (MEDI-538; anti-CD19 BiTE) in patients with relapsed B-NHL: data from dose-escalation study MT103-104. Blood (ASH Annual Meeting Abstracts). 2006;108:Abstract 2725.","DOI":"10.1182\/blood.V108.11.2725.2725"},{"key":"405_CR42","doi-asserted-by":"crossref","unstructured":"G\u00f6kbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Havelange V, et al. BLAST: a confirmatory, single-arm, phase 2 study of blinatumomab, a bispecific T-cell engager (BiTE\u00ae) antibody construct, in patients with minimal residual disease B-precursor acute lymphoblastic leukemia (ALL). Blood (ASH Annual Meeting Abstracts). 2014;124:Abstract 379.","DOI":"10.1182\/blood.V124.21.379.379"},{"key":"405_CR43","doi-asserted-by":"crossref","unstructured":"Schub A, Nagele V, Zugmaier G, Brandl C, Hijazi Y, Topp MS, et al. Immunopharmacodynamic response to blinatumomab in patients with relapsed\/refractory B-precursor acute lymphoblastic leukemia (ALL). J Clin Oncol. 2013;31(15 suppl):Abstract 7020.","DOI":"10.1200\/jco.2013.31.15_suppl.7020"},{"key":"405_CR44","doi-asserted-by":"crossref","unstructured":"Viardot A, Goebeler M, Hess G, Neumann S, Pfreundschuh M, Adrian N, et al. Treatment of relapsed\/refractory diffuse large B-cell lymphoma with the bispecific T-cell engager (BiTE\u00ae) antibody construct blinatumomab: primary analysis results from an open-label, phase 2 study. Blood (ASH Annual Meeting Abstracts). 2014;124:Abstract 4460.","DOI":"10.1182\/blood.V124.21.4460.4460"}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-016-0405-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40262-016-0405-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-016-0405-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-016-0405-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:05:38Z","timestamp":1600646738000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40262-016-0405-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,21]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["405"],"URL":"https:\/\/doi.org\/10.1007\/s40262-016-0405-4","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,21]]}}}