{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:53:57Z","timestamp":1781690037401,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Quantitative modeling can guide drug development and regulatory decisions by providing insights into pharmacokinetics, pharmacodynamics, efficacy, and safety. Integrating models allows simulations that support dosing considerations. A simulation framework for belantamab mafodotin (B) in relapsed\/refractory multiple myeloma was developed using data from monotherapy studies and combination studies with bortezomib\/dexamethasone (BVd) and pomalidomide\/dexamethasone (BPd). Individual changes from baseline in serum M\u2010protein concentrations were modeled using a tumor growth inhibition model. Changes in ophthalmic exam findings (OEFs) grades per the Keratopathy and Visual Acuity (KVA) scale were modeled using a continuous\u2010time Markov model. Belantamab mafodotin concentrations were modeled with a population pharmacokinetic model. All final models adequately described the clinical data. The M\u2010protein\/KVA\/pharmacokinetic models were integrated in a simulation framework, and simulations of treatment outcomes were performed. Simulated regimens included dose modifications (holds\/reductions) for OEFs. Simulations of protocol dosing and dose modifications from the phase 3 DREAMM\u20107 (BVd) and DREAMM\u20108 (BPd) trials predicted similar results to the respective trials (for BVd simulations\/DREAMM\u20107 data: very good partial response rates [VGPR+] 62.0%\/62.0%, median progression\u2010free survival [mPFS] 39.4\/36.6\u2009months, and grade \u2265\u20093 OEFs 87.5%\/76.5%; for BPd simulations\/DREAMM\u20108 data: VGPR+ rates 60.2%\/68.0%, mPFS not reached\/not reached, and grade \u2265\u20093 OEFs 77.2%\/82.5%). Simulations of alternative BVd regimens indicated that a 2.5\u2009mg\/kg starting dose produces the highest efficacy, and schedule extensions after the first BVd dose can improve tolerability while continuing to demonstrate efficacy. This framework adequately predicted outcomes from DREAMM\u20107\/DREAMM\u20108, supporting its use to predict benefit\u2013risk profiles of alternate belantamab mafodotin dosing strategies.<\/jats:p>","DOI":"10.1002\/psp4.70276","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:50:29Z","timestamp":1780627829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simulation Framework to Investigate Efficacy and Ocular Safety of Belantamab Mafodotin Combinations in Relapsed\/Refractory Multiple Myeloma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-5235","authenticated-orcid":false,"given":"Fernando","family":"Carre\u00f1o","sequence":"first","affiliation":[{"name":"GSK  Upper Providence Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7016-2846","authenticated-orcid":false,"given":"Martijn","family":"van Noort","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The\u00a0Netherlands"}],"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":"Stefan","family":"Zeiser","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2691-9392","authenticated-orcid":false,"given":"Theodoros","family":"Papathanasiou","sequence":"additional","affiliation":[{"name":"GSK  Baar Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-2678","authenticated-orcid":false,"given":"Teun M.","family":"Post","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0718-1735","authenticated-orcid":false,"given":"Yi Ting (Kayla)","family":"Lien","sequence":"additional","affiliation":[{"name":"GSK  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0074-1938","authenticated-orcid":false,"given":"Yu Liu","family":"Ho","sequence":"additional","affiliation":[{"name":"GSK  Upper Providence Pennsylvania 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  Upper Providence Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Food and Drug Administration \u201cOptimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases \u201daccessed September 12 2025 https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/optimizing\u2010dosage\u2010human\u2010prescription\u2010drugs\u2010and\u2010biological\u2010products\u2010treatment\u2010oncologic\u2010diseases."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13027"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201021\u20100035"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102013\u201010\u2010535088"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20103026(23)00243\u20100"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(19)30788\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34987"},{"key":"e_1_2_10_9_1","unstructured":"ClinicalTrials.gov \u201cTo Evaluate Safety Tolerability and Clinical Activity of the Antibody\u2010Drug Conjugate GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A) or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed\/Refractory Multiple Myeloma (RRMM) (DREAMM 6) \u201daccessed September 4 2025 https:\/\/clinicaltrials.gov\/study\/NCT03544281."},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102020\u2010139332"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(25)00330\u20104"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2405090"},{"key":"e_1_2_10_13_1","first-page":"846","article-title":"Updated Results From Phase 3 DREAMM\u20108 Study of Belantamab Mafodotin Plus Pomalidomide and Dexamethasone vs Pomalidomide Plus Bortezomib and Dexamethasone in Relapsed\/Refractory Multiple Myeloma","volume":"9","author":"Dimopoulos M. 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