{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:13:24Z","timestamp":1790702004922,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To characterize the pharmacokinetics (PK) of moxetumomab pasudotox, an anti\u2010CD22 recombinant immunotoxin, in adults with relapsed or refractory hairy cell leukaemia, we examined data from a phase 1 study (Study 1001; <jats:italic>n<\/jats:italic> = 49) and from the pivotal clinical study (Study 1053; <jats:italic>n<\/jats:italic> = 74).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from both studies were pooled (<jats:italic>n<\/jats:italic> = 123) to develop a population PK model. Covariates included demographics, disease state, liver and kidney function, prior treatment, and antidrug antibodies (ADAs). Exposure\u2013response and exposure\u2013safety were analysed separately by study. A 1\u2010compartment model with linear elimination from the central compartment and 2 clearance (CL) rates was developed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Moxetumomab pasudotox was cleared more rapidly after cycle 1, day 1 (CL<jats:sub>1<\/jats:sub> = 24.7 L\/h) than subsequently (CL<jats:sub>2<\/jats:sub> = 3.76 L\/h), with high interindividual variability (116 and 109%, respectively). In Study 1053, patients with ADA titres &gt;10 240 showed ~4\u2010fold increase in CL. Higher exposures (\u2265median) were related to higher response rates, capillary leak syndrome and increased creatinine (Study 1053 only), or grade \u22653 adverse events (Study 1001 only). Clinical benefits were still observed in patients with lower exposure or high ADA titres.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite a high incidence of immunogenicity with increased clearance, moxetumomab pasudotox demonstrated efficacy in hairy cell leukaemia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14250","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T07:42:48Z","timestamp":1582184568000},"page":"1367-1376","source":"Crossref","is-referenced-by-count":14,"title":["Population pharmacokinetics, efficacy, and safety of moxetumomab pasudotox in patients with relapsed or refractory hairy cell leukaemia"],"prefix":"10.1111","volume":"86","author":[{"given":"Denison","family":"Kuruvilla","sequence":"first","affiliation":[{"name":"AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen Lin","family":"Chia","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemal","family":"Balic","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai Shun","family":"Yao","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Kreitman","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Pastan","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Standifer","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meina","family":"Liang","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Ming","family":"Tseng","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Faggioni","sequence":"additional","affiliation":[{"name":"AstraZeneca  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorin","family":"Roskos","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-689422"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V13.7.609.609"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-508754"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25243"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07668.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14524"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2014-0358"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation.V2012.1.660.3798659"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2015.09.003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.2630"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107263450402"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.8.1622"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0487"},{"key":"e_1_2_10_15_1","unstructured":"Lumoxiti [package insert]. 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