{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:58:01Z","timestamp":1790927881401,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"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":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Model\u2010informed drug development is increasingly used to support chimeric antigen receptor (CAR)\u2010T\u2010cell therapy programs. However, most population pharmacokinetic (PK) CAR\u2010T\u2010cell models available in literature are variations of an empirical piecewise\u2010linear model, which accurately describes the observed data but lacks a mechanistic foundation. This limits its use for simulations of scenarios beyond the observed data. This work presents a mechanism\u2010based population PK framework that aims to bridge existing empirical and mechanistic CAR\u2010T\u2010cell modeling approaches. The model was developed using a clinical database of 473 patients with various relapsed or refractory lymphomas (large B cell, follicular, marginal zone, or mantle cell) receiving axicabtagene ciloleucel or brexucabtagene autoleucel. The framework incorporates two CAR\u2010T\u2010cell compartments alongside a latent kinetic\u2010pharmacodynamic tumor compartment, utilizing a continuous, mechanistically\u2010driven approach to characterize the observed PK profiles. A covariate search identified five significant covariates impacting PK (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Among these, only product type\/mantle cell lymphoma (MCL) disease type was deemed to have clinically relevant effects on exposure. Despite its mechanistic basis, the model remains parsimonious, requiring only seven structural parameters, and no additional data beyond post\u2010infusion CAR\u2010T\u2010cell peripheral blood concentrations and covariate information routinely collected in clinical trials. With its mechanistic foundation but parsimonious structure, this model balances data\u2010driven practicality with the integration of underlying biological processes. Its ability to identify relevant covariates could make it a valuable tool in supporting drug development decisions.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70395","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:37:42Z","timestamp":1784691462000},"page":"1027-1040","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Model\u2010Based Analysis with Mechanistic Insights to\n                    <scp>CAR<\/scp>\n                    \u2010T\u2010Cell Therapy Kinetics: Case Study with Axicabtagene Ciloleucel and Brexucabtagene Autoleucel"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5936-1877","authenticated-orcid":false,"given":"Anna M.","family":"Mc Laughlin","sequence":"first","affiliation":[{"name":"Pharmetheus AB  Uppsala 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