{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:27:43Z","timestamp":1791613663826,"version":"4.3.4"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1007\/s40262-025-01531-2","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T17:51:19Z","timestamp":1748973079000},"page":"1119-1132","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Population Cellular Kinetics of Idecabtagene Vicleucel in Patients with Triple-Class\u2013Exposed Relapsed\/Refractory Multiple Myeloma"],"prefix":"10.1007","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-4049","authenticated-orcid":false,"given":"Fan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xirong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhan","family":"Masilamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Caia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Piasecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Lamba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"issue":"1","key":"1531_CR1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41408-024-01115-6","volume":"14","author":"M Mohty","year":"2024","unstructured":"Mohty M, et al. A roadmap towards improving outcomes in multiple myeloma. Blood Cancer J. 2024;14(1):135.","journal-title":"Blood Cancer J"},{"issue":"17","key":"1531_CR2","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.3390\/cancers16172931","volume":"16","author":"DS Parekh","year":"2024","unstructured":"Parekh DS, et al. Updates on therapeutic strategies in the treatment of relapsed\/refractory multiple myeloma. Cancers. 2024;16(17):2931.","journal-title":"Cancers"},{"issue":"27","key":"1531_CR3","doi-asserted-by":"publisher","first-page":"4416","DOI":"10.1200\/JCO.23.00512","volume":"41","author":"SA Holstein","year":"2023","unstructured":"Holstein SA, Grant SJ, Wildes TM. Chimeric antigen receptor T-cell and bispecific antibody therapy in multiple myeloma: moving into the future. J Clin Oncol. 2023;41(27):4416\u201329.","journal-title":"J Clin Oncol"},{"key":"1531_CR4","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2024.12.001","author":"TH Mouhieddine","year":"2024","unstructured":"Mouhieddine TH, Costa BA, Richter J. Advancements in bispecific antibodies for multiple myeloma: what\u2019s new and what lies ahead. Semin Hematol. 2024. https:\/\/doi.org\/10.1053\/j.seminhematol.2024.12.001.","journal-title":"Semin Hematol"},{"issue":"5","key":"1531_CR5","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1089\/hum.2018.001","volume":"29","author":"KM Friedman","year":"2018","unstructured":"Friedman KM, et al. Effective Targeting of multiple B-cell maturation antigen-expressing hematological malignances by anti-b-cell maturation antigen chimeric antigen receptor T cells. Hum Gene Ther. 2018;29(5):585\u2013601.","journal-title":"Hum Gene Ther"},{"key":"1531_CR6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024582","author":"S Ailawadhi","year":"2024","unstructured":"Ailawadhi S, et al. Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. Blood. 2024. https:\/\/doi.org\/10.1182\/blood.2024024582.","journal-title":"Blood"},{"issue":"11","key":"1531_CR7","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1056\/NEJMoa2213614","volume":"388","author":"P Rodriguez-Otero","year":"2023","unstructured":"Rodriguez-Otero P, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002\u201314.","journal-title":"N Engl J Med"},{"issue":"8","key":"1531_CR8","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1056\/NEJMoa2024850","volume":"384","author":"NC Munshi","year":"2021","unstructured":"Munshi NC, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705\u201316.","journal-title":"N Engl J Med"},{"key":"1531_CR9","unstructured":"FDA, Package insert and medication guide\u2014ABECMA. 2024."},{"key":"1531_CR10","unstructured":"EMA, ABECMA\u2014Summary of product characteristics. 2024."},{"issue":"3","key":"1531_CR11","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1002\/cpt.2040","volume":"109","author":"C Liu","year":"2021","unstructured":"Liu C, et al. Model-based cellular kinetic analysis of chimeric antigen receptor-T cells in humans. Clin Pharmacol Ther. 2021;109(3):716\u201327.","journal-title":"Clin Pharmacol Ther"},{"key":"1531_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114421","volume":"188","author":"T Qi","year":"2022","unstructured":"Qi T, et al. Cellular kinetics: a clinical and computational review of CAR-T cell pharmacology. Adv Drug Deliv Rev. 2022;188: 114421.","journal-title":"Adv Drug Deliv Rev"},{"key":"1531_CR13","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jtbi.2012.12.025","volume":"327","author":"RJ De Boer","year":"2013","unstructured":"De Boer RJ, Perelson AS. Quantifying T lymphocyte turnover. J Theor Biol. 2013;327:45\u201387.","journal-title":"J Theor Biol"},{"issue":"12","key":"1531_CR14","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1007\/s40262-021-01039-5","volume":"60","author":"K Ogasawara","year":"2021","unstructured":"Ogasawara K, et al. Population cellular kinetics of lisocabtagene maraleucel, an autologous CD19-directed chimeric antigen receptor T-cell product, in patients with relapsed\/refractory large B-cell lymphoma. Clin Pharmacokinet. 2021;60(12):1621\u201333.","journal-title":"Clin Pharmacokinet"},{"issue":"5","key":"1531_CR15","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/psp4.12388","volume":"8","author":"AM Stein","year":"2019","unstructured":"Stein AM, et al. Tisagenlecleucel model-based cellular kinetic analysis of chimeric antigen receptor-T Cells. CPT Pharmacometrics Syst Pharmacol. 2019;8(5):285\u201395.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"45","key":"1531_CR16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2305774120","volume":"120","author":"R Straube","year":"2023","unstructured":"Straube R, Schmidt BJ. A mean-field description for the expansion kinetics of activated T cell populations. Proc Natl Acad Sci USA. 2023;120(45): e2305774120.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1531_CR17","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-2753","author":"H Hu","year":"2025","unstructured":"Hu H, et al. Population pharmacokinetics of orvacabtagene autoleucel, an autologous BCMA-directed chimeric antigen receptor T-cell product, in patients with relapsed\/refractory multiple myeloma. Clin Cancer Res. 2025. https:\/\/doi.org\/10.1158\/1078-0432.CCR-24-2753.","journal-title":"Clin Cancer Res"},{"issue":"9","key":"1531_CR18","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1111\/cts.13349","volume":"15","author":"J Kast","year":"2022","unstructured":"Kast J, et al. Recent advances and clinical pharmacology aspects of chimeric antigen receptor (CAR) T-cellular therapy development. Clin Transl Sci. 2022;15(9):2057\u201374.","journal-title":"Clin Transl Sci"},{"key":"1531_CR19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.7527","author":"EG Thompson","year":"2024","unstructured":"Thompson EG, et al. Association of patient (pt) factors and pharmacodynamic biomarkers with progression-free survival (PFS) after idecabtagene vicleucel (ide-cel) in pts from KarMMa-3. Am Soc Clin Oncol. 2024. https:\/\/doi.org\/10.1200\/JCO.2024.42.16_suppl.7527.","journal-title":"Am Soc Clin Oncol"},{"key":"1531_CR20","doi-asserted-by":"crossref","unstructured":"Wu, F., et al., Characterizing cellular kinetics of idecabtagene vicleucel in patients with triple-class-exposed relapsed\/refractory multiple myeloma. In: ASCPT annual meeting. 2024: Colorado Springs, CO.","DOI":"10.1007\/s40262-025-01531-2"},{"key":"1531_CR21","doi-asserted-by":"crossref","unstructured":"Wu, F., et al. Population cellular kinetics of idecabtagene vicleucel in patients with triple-class-exposed relapsed\/refractory multiple myeloma. In: 15th annual american conference on pharmacometrics. 2024. Phoenix, Arizona.","DOI":"10.1007\/s40262-025-01531-2"},{"issue":"9","key":"1531_CR22","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1038\/s41591-023-02496-0","volume":"29","author":"Y Lin","year":"2023","unstructured":"Lin Y, et al. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Nat Med. 2023;29(9):2286\u201394.","journal-title":"Nat Med"},{"issue":"3","key":"1531_CR23","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1002\/cpt.2991","volume":"114","author":"M Masilamani","year":"2023","unstructured":"Masilamani M, et al. Bioanalytical methods for characterization of CAR-T cellular kinetics: comparison of PCR assays and matrices. Clin Pharmacol Ther. 2023;114(3):664\u201372.","journal-title":"Clin Pharmacol Ther"},{"key":"1531_CR24","unstructured":"FDA, Immunogenicity testing of therapeutic protein products\u2014developing and validating assays for anti-drug antibody detection\u2014guidance for industry. 2019."},{"issue":"2","key":"1531_CR25","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1208\/s12248-009-9112-5","volume":"11","author":"M Bergstrand","year":"2009","unstructured":"Bergstrand M, Karlsson MO. Handling data below the limit of quantification in mixed effect models. AAPS J. 2009;11(2):371\u201380.","journal-title":"AAPS J"},{"issue":"8","key":"1531_CR26","doi-asserted-by":"publisher","first-page":"e328","DOI":"10.1016\/S1470-2045(16)30206-6","volume":"17","author":"S Kumar","year":"2016","unstructured":"Kumar S, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328\u201346.","journal-title":"Lancet Oncol"},{"issue":"11","key":"1531_CR27","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1002\/psp4.12922","volume":"12","author":"JN Connarn","year":"2023","unstructured":"Connarn JN, et al. Characterizing the exposure-response relationship of idecabtagene vicleucel in patients with relapsed\/refractory multiple myeloma. CPT Pharmacometrics Syst Pharmacol. 2023;12(11):1687\u201397.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"1","key":"1531_CR28","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1056\/NEJMoa1804980","volume":"380","author":"SJ Schuster","year":"2019","unstructured":"Schuster SJ, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. New Engl J Med. 2019;380(1):45\u201356.","journal-title":"New Engl J Med"},{"issue":"4","key":"1531_CR29","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/psp4.12500","volume":"9","author":"P Traynard","year":"2020","unstructured":"Traynard P, et al. Efficient pharmacokinetic modeling workflow with the monolixsuite: a case study of remifentanil. CPT Pharmacometrics Syst Pharmacol. 2020;9(4):198\u2013210.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"6213","key":"1531_CR30","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1126\/science.1260044","volume":"346","author":"JM Marchingo","year":"2014","unstructured":"Marchingo JM, et al. T cell signalling. Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion. Science. 2014;346(6213):1123\u20137.","journal-title":"Science"},{"issue":"5","key":"1531_CR31","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/87730","volume":"2","author":"MJ van Stipdonk","year":"2001","unstructured":"van Stipdonk MJ, Lemmens EE, Schoenberger SP. Naive CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation. Nat Immunol. 2001;2(5):423\u20139.","journal-title":"Nat Immunol"},{"key":"1531_CR32","unstructured":"Cheng, Y., et al. Population cellular kinetics of orvacabtagene autoleucel, an autologous bcma-directed chimeric antigen receptor T-cell product, in patients with relapsed\/refractory multiple myeloma. In: 15th annual american conference on pharmacometrics. 2024. Phoenix, Arizona."},{"issue":"9","key":"1531_CR33","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1111\/bcp.14281","volume":"86","author":"N Dasyam","year":"2020","unstructured":"Dasyam N, George P, Weinkove R. Chimeric antigen receptor T-cell therapies: optimising the dose. Br J Clin Pharmacol. 2020;86(9):1678\u201389.","journal-title":"Br J Clin Pharmacol"},{"issue":"18","key":"1531_CR34","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1056\/NEJMoa1817226","volume":"380","author":"N Raje","year":"2019","unstructured":"Raje N, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. New Engl J Med. 2019;380(18):1726\u201337.","journal-title":"New Engl J Med"},{"key":"1531_CR35","unstructured":"Zhou J, Burnett J, Zheng X, Chen Y, Caia A, Cook M, Kondic A, Lamba M, Wu F. Characterizing exposure-response relationships of idecabtagene vicleucel in patients with triple-class\u2013exposed relapsed\/refractory multiple myeloma. In: The American Society for Clinical Pharmacology and Therapeutics (ASCPT). 2024. Colorado Springs, CO."},{"key":"1531_CR36","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1007\/s40262-018-0715-9","volume":"58","author":"JB Langenhorst","year":"2019","unstructured":"Langenhorst JB, et al. Population pharmacokinetics of fludarabine in children and adults during conditioning prior to allogeneic hematopoietic cell transplantation. Clin Pharmacokinet. 2019;58:627\u201337.","journal-title":"Clin Pharmacokinet"},{"issue":"4","key":"1531_CR37","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1046\/j.1523-1755.2002.00279.x","volume":"61","author":"M Haubitz","year":"2002","unstructured":"Haubitz M, et al. Cyclophosphamide pharmacokinetics and dose requirements in patients with renal insufficiency. Kidney Int. 2002;61(4):1495\u2013501.","journal-title":"Kidney Int"},{"issue":"3","key":"1531_CR38","doi-asserted-by":"publisher","first-page":"777","DOI":"10.3324\/haematol.2023.283940","volume":"109","author":"S Sidana","year":"2023","unstructured":"Sidana S, et al. Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed\/refractory multiple myeloma with renal impairment. Haematologica. 2023;109(3):777.","journal-title":"Haematologica"},{"key":"1531_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.886546","volume":"13","author":"AN Khan","year":"2022","unstructured":"Khan AN, et al. Immunogenicity of CAR-T cell therapeutics: evidence, mechanism and mitigation. Front Immunol. 2022;13: 886546.","journal-title":"Front Immunol"},{"key":"1531_CR40","unstructured":"FDA, Summary basis for regulatory action\u2014ABECMA. 2024."},{"issue":"1","key":"1531_CR41","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","volume":"15","author":"SS Neelapu","year":"2018","unstructured":"Neelapu SS, et al. Chimeric antigen receptor T-cell therapy\u2014assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47\u201362.","journal-title":"Nat Rev Clin Oncol"},{"issue":"24","key":"1531_CR42","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1182\/blood.2024024381","volume":"144","author":"K Maurer","year":"2024","unstructured":"Maurer K, et al. Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma. Blood. 2024;144(24):2490\u2013502.","journal-title":"Blood"}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01531-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-025-01531-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01531-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T14:56:42Z","timestamp":1750690602000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-025-01531-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,3]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["1531"],"URL":"https:\/\/doi.org\/10.1007\/s40262-025-01531-2","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,3]]},"assertion":[{"value":"14 May 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"F.W., J.Z., X.Z., M.M., and Y.C. wrote the manuscript; F.W. and M.L. designed the research; F.W., A.C., M.C., and J.P. performed the research; F.W., J.Z., and X.Z. analysed the data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}},{"value":"The authors thank Yan Li, Ken Ogasawara, Hongxiang Hu, Li Zhu, Roxanne Cacioppo, John Calhoun, and Bindu Murthy for their review comments during the preparation of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"This study was funded by Bristol Myers Squibb.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Bristol Myers Squibb policy on data sharing may be found at .","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data, Code, and Material"}},{"value":"F.W., J. Z., X.Z., M.M., Y.C., A.C., M.C., J.P., and M.L. were employees and stockholders of Bristol Myers Squibb during the preparation of the manuscript. F.W. is currently affiliated with Deerfield Management, and M.L. is currently affiliated with Pfizer.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The research was conducted within all the appropriate ethical and legal guidelines. The KarMMa-3 study protocol was approved by the institutional review board or independent ethics committee at each participating center before trial initiation (study start date of 16 April 2019).","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"For investigations involving human patients, informed consent was obtained from the participants involved.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"All authors approved this manuscript for submission.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}]}}