{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:19:33Z","timestamp":1783948773563,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"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;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study demonstrates the application of a model based meta analysis (MBMA) framework to characterize the safety and efficacy profiles of therapies in relapsed and refractory multiple myeloma (RRMM). Published clinical trial data were analyzed to evaluate the incidence of Grade \u2265\u20093 neutropenia and overall response rate (ORR), providing a quantitative foundation for model\u2010informed drug development. The final model incorporated trial\u2010 and treatment\u2010level covariates and was evaluated using visual predictive checks and predictive simulations. Results revealed increased neutropenia risk associated with alkylating agents and higher ORR in regimens with background corticosteroids and in patients with only one prior line of therapy. MBMA\u2010derived estimates facilitated systematic comparisons across regimens, accounting for heterogeneity in trial design and populations. The MBMA estimates can also support benchmarking of internal regimens against current standards. A quantitative systems pharmacology (QSP) model, developed in parallel, was also used to simulate patient responses across a broad array of RRMM treatments, including novel combinations involving T\u2010cell engagers (TCEs) and CELMoD agents. Trial\u2010calibrated virtual patients and a classifier for prior therapy exposure enabled the prediction of regimen\u2010specific ORR across different treatment histories. Together, the MBMA\u2010informed and QSP\u2010supported modeling strategy enabled a comprehensive benefit\u2013risk assessment by combining statistical estimation with mechanistic simulation. This coordinated approach enhances clinical decision\u2010making by enabling comparison of novel or investigational therapies to the evolving treatment landscape, particularly in the absence of head\u2010to\u2010head trials.<\/jats:p>","DOI":"10.1002\/psp4.70145","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:44:18Z","timestamp":1762857858000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating\n                    <scp>MBMA<\/scp>\n                    and\n                    <scp>QSP<\/scp>\n                    to Identify Key Covariates and Predict Treatment Outcomes in Relapsed\/Refractory Multiple Myeloma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6853-664X","authenticated-orcid":false,"given":"Zeel","family":"Shah","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton M.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Simulations Plus  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"McCormick","sequence":"additional","affiliation":[{"name":"Simulations Plus  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Vallejo","sequence":"additional","affiliation":[{"name":"Simulations Plus  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Duncan","sequence":"additional","affiliation":[{"name":"Simulations Plus  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7812-2778","authenticated-orcid":false,"given":"Chuanpu","family":"Hu","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-4084","authenticated-orcid":false,"given":"Alexander V.","family":"Ratushny","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna G.","family":"Kondic","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100808"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12041"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010022\u201003201\u20105"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12049"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174320"},{"key":"e_1_2_9_7_1","unstructured":"Certara \u201cCoDEx: Clinical Trial Outcomes Databases \u201d(2025) https:\/\/www.certara.com\/codex\u2010clinical\u2010trial\u2010outcomes\u2010databases\/."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4040"},{"key":"e_1_2_9_9_1","unstructured":"Lixoft \u201cCase Study: Longitudinal Model Based Meta Analysis. Simulations Plus \u201d(2025) https:\/\/monolixsuite.slp\u2010software.com\/tutorials\/2024R1\/time\u2010to\u2010event\u2010modeling\u2010with\u2010the\u2010monolixsuite\u2010intro."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(16)30206\u20106"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010022\u201009817\u20109"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12286"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.03021"},{"key":"e_1_2_9_14_1","unstructured":"Society ACandAmerican Cancer Society \u201cStaging Multiple Myeloma \u201d(2025) https:\/\/www.cancer.org\/cancer\/types\/multiple\u2010myeloma\/detection\u2010diagnosis\u2010staging\/staging.html."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27973"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/CPAA.S62512"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.15440"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018022806"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201011\u2010124156"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13102465"},{"issue":"12","key":"e_1_2_9_21_1","first-page":"765","article-title":"Drug\u2010Induced Neutropenia: A Focus on Rituximab\u2010Induced Late\u2010Onset Neutropenia","volume":"41","author":"Moore D. C.","year":"2016","journal-title":"P T"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.4102\/hsag.v28i0.2221"},{"key":"e_1_2_9_23_1","unstructured":"N. I.Silico \u201cCoupling a QSP Model With a Simple Statistical Layer to Predict Asthma Exacerbation Rate Reduction From Allergen Challenge Results. Presented at: ACOP15; November 10th\u201013th 2024 2024; Phoenix AZ \u201d(2024) https:\/\/www.novainsilico.ai\/wp\u2010content\/uploads\/2024\/12\/Poster_ACOP15_AsthmaExacerbation.pdf."},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12633"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70145","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70145","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:18:22Z","timestamp":1773029902000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/psp4.70145"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70145","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]},"assertion":[{"value":"2025-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70145"}}