{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:51:31Z","timestamp":1792068691417,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>A simultaneous pharmacokinetic (PK)\/pharmacodynamic (PD) analysis was conducted to characterize relationships between anti\u2010B\u2010cell maturation antigen (BCMA)\u2010targeting antibody\u2010drug conjugate, belantamab mafodotin, and longitudinal multiple myeloma (MM) disease markers (soluble BCMA [sBCMA], M\u2010protein). Data from patients with relapsed\/refractory MM receiving belantamab mafodotin monotherapy in the DREAMM\u20101 (NCT02064387), DREAMM\u20102 (NCT03525678), DREAMM\u20103 (NCT04162210), or DREAMM\u20105 (NCT04126200) trials were included. The dataset contained 510 patients with 15,860 PK and PD observations. Previous population PK and M\u2010protein PD models were combined to create a new starting model. Overparameterization was reduced using sensitivity analyses to create a 2\u2010compartment base model for belantamab mafodotin with a linear clearance component and target\u2010mediated drug disposition assuming quasi\u2010equilibrium between belantamab mafodotin and sBCMA binding. Free belantamab mafodotin affected M\u2010protein elimination rate via a direct effect, and M\u2010protein in turn scaled sBCMA synthesis rate. sBCMA was assumed to transfer into the central free sBCMA compartment through a reservoir compartment, allowing capture of observed differences in timescales. Stepwise covariate modeling led to the final model, which contained eight covariate effects (baseline sBCMA, albumin, body weight, and sex on belantamab mafodotin clearance; baseline body weight and sex on belantamab mafodotin central volume of distribution; extramedullary disease at screening and baseline sBCMA on M\u2010protein death rate constant). Simulations of belantamab mafodotin doses\/schedules showed concentrations of free sBCMA and M\u2010protein decreased as free and total belantamab mafodotin increased with higher doses. The PKPD model captured the clearance of belantamab mafodotin and the highly dynamic interactions between belantamab mafodotin PK, M\u2010protein, and sBCMA.<\/jats:p>","DOI":"10.1002\/psp4.70337","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:02:14Z","timestamp":1790740934000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simultaneous Population\n                    <scp>PKPD<\/scp>\n                    Analysis of Belantamab Mafodotin, Soluble\n                    <scp>BCMA<\/scp>\n                    , and Serum M\u2010Protein in Relapsed\/Refractory Multiple Myeloma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5744-3249","authenticated-orcid":false,"given":"John D.","family":"Clements","sequence":"first","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-3746","authenticated-orcid":false,"given":"Inmaculada C.","family":"Sorribes","sequence":"additional","affiliation":[{"name":"Certara Drug Development Solutions Certara USA, Inc.  Radnor Pennsylvania USA"},{"name":"Quantitative Pharmacology and Pharmacometrics Immune\/Oncology (QP2\u2010I\/O) Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Kaullen","sequence":"additional","affiliation":[{"name":"Certara Drug Development Solutions Certara USA, Inc.  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3915-9229","authenticated-orcid":false,"given":"Christine","family":"Neumar","sequence":"additional","affiliation":[{"name":"Certara Drug Development Solutions Certara USA, Inc.  Radnor Pennsylvania USA"},{"name":"Quantitative Clinical Pharmacology Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7373-5660","authenticated-orcid":false,"given":"Adekemi","family":"Taylor","sequence":"additional","affiliation":[{"name":"Certara Drug Development Solutions Certara USA, Inc.  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mun Sang","family":"Yue","sequence":"additional","affiliation":[{"name":"Certara Drug Development Solutions Certara USA, Inc.  Radnor Pennsylvania USA"},{"name":"Exelixis Inc  Alameda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3011-1572","authenticated-orcid":false,"given":"Herbert","family":"Struemper","sequence":"additional","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-8315","authenticated-orcid":false,"given":"Geraldine","family":"Ferron\u2010Brady","sequence":"additional","affiliation":[{"name":"GSK, Clinical Pharmacology Modeling and Simulation  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30206-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00408-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12836"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0035"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0734-z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024026028"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-211840"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.150896"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.15.77"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(23)00243-0"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30788-0"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2020-1269"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30576-X"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2403407"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2405090"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-200336"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-019-0196-6"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34987"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-129879"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2152-2650(21)02339-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.8019"},{"key":"e_1_2_11_23_1","article-title":"P913: Low\u2010Dose Belantamab Mafodotin (Belamaf) in Combination With Nirogacestat vs Belamaf Monotherapy in Patients With Relapsed\/Refractory Multiple Myeloma (RRMM): Phase 1\/2 DREAMM\u20105 Platform Sub\u2010Study 3","volume":"7","author":"Paul C. N. R.","year":"2023","journal-title":"HemaSphere"},{"key":"e_1_2_11_24_1","unstructured":"GSK \u201cBlenrep (Belantamab Mafodotin) Combinations Approved by UK MHRA in Relapsed\/Refractory Multiple Myeloma \u201dhttps:\/\/www.gsk.com\/en\u2010gb\/media\/press\u2010releases\/blenrep\u2010belantamab\u2010mafodotin\u2010combinations\u2010approved\u2010by\u2010uk\u2010mhra\u2010in\u2010relapsedrefractory\u2010multiple\u2010myeloma\/."},{"key":"e_1_2_11_25_1","unstructured":"European Medicines Agency \u201cBlenrep \u201dhttps:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/blenrep\u20100#:~:text=On%2022%20May%202025%2C%20the relapsed%20or%20refractory%20multiple%20myeloma."},{"key":"e_1_2_11_26_1","unstructured":"GSK \u201cBlenrep (Belantamab Mafodotin) Combinations Approved in Japan for Treatment of Relapsed\/Refractory Multiple Myeloma \u201dhttps:\/\/www.gsk.com\/en\u2010gb\/media\/press\u2010releases\/blenrep\u2010belantamab\u2010mafodotin\u2010combinations\u2010approved\u2010in\u2010japan\/."},{"key":"e_1_2_11_27_1","unstructured":"GSK \u201cBlenrep (Belantamab Mafodotin) Combinations Approved in Canada for the Treatment of Relapsed\/Refractory Multiple Myeloma \u201dhttps:\/\/ca.gsk.com\/en\u2010ca\/media\/press\u2010releases\/blenrep\u2010belantamab\u2010mafodotin\u2010combinations\u2010approved\u2010in\u2010canada\u2010for\u2010the\u2010treatment\u2010of\u2010relapsedrefractory\u2010multiple\u2010myeloma\/Accessed."},{"key":"e_1_2_11_28_1","unstructured":"GSK \u201cGSK Announces Extension of US Food and Drug Administration Review Period for Blenrep (Belantamab Mafodotin\u2010Blmf) in Relapsed\/Refractory Multiple Myeloma \u201dhttps:\/\/ca.gsk.com\/en\u2010ca\/media\/press\u2010releases\/blenrep\u2010belantamab\u2010mafodotin\u2010combinations\u2010approved\u2010in\u2010canada\u2010for\u2010the\u2010treatment\u2010of\u2010relapsedrefractory\u2010multiple\u2010myeloma\/."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-178026"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12660"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13016"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-025-01508-1"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2019.0722"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081872"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v045.i03"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.41"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-023-00989-z"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.803693"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12815"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-198720"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2409"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-025-01174-0"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-023-00788-4"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3663"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012999.36063.4e"},{"key":"e_1_2_11_46_1","unstructured":"ClinicalTrials.gov \u201cA Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments (DREAMM\u201020) \u201dhttps:\/\/clinicaltrials.gov\/study\/NCT05714839."},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000970836.36618.0e"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70337","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70337","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70337","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:18:05Z","timestamp":1792066685000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":46,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/psp4.70337"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70337","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2025-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70337"}}