Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation
IntroductionDiscontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment fre...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1028871/full |
| _version_ | 1811208526413955072 |
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| author | Elena Karg Christoph Baldow Thomas Zerjatke Richard E. Clark Ingo Roeder Ingo Roeder Artur C. Fassoni Ingmar Glauche |
| author_facet | Elena Karg Christoph Baldow Thomas Zerjatke Richard E. Clark Ingo Roeder Ingo Roeder Artur C. Fassoni Ingmar Glauche |
| author_sort | Elena Karg |
| collection | DOAJ |
| description | IntroductionDiscontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment free remission (TFR). However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials.MethodsHere, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success.ResultsOur systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI.DiscussionOur findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients. |
| first_indexed | 2024-04-12T04:22:55Z |
| format | Article |
| id | doaj.art-02f53142ebb54357bbd60724872348d6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T04:22:55Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-02f53142ebb54357bbd60724872348d62022-12-22T03:48:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-12-011210.3389/fonc.2022.10288711028871Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessationElena Karg0Christoph Baldow1Thomas Zerjatke2Richard E. Clark3Ingo Roeder4Ingo Roeder5Artur C. Fassoni6Ingmar Glauche7Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyInstitute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyInstitute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyDepartment of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United KingdomInstitute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyNational Center for Tumor Diseases (NCT), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden–Rossendorf (HZDR), Dresden, GermanyInstituto de Matemática e Computação, Universidade Federal de Itajubá (UNIFEI), Itajubá, BrazilInstitute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyIntroductionDiscontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment free remission (TFR). However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials.MethodsHere, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success.ResultsOur systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI.DiscussionOur findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.1028871/fullchronic myeloid leukaemia (CML)treatment free remission (TFR)dose reductiontyrosine kinase inhibitor (TKI)mathematical modelling |
| spellingShingle | Elena Karg Christoph Baldow Thomas Zerjatke Richard E. Clark Ingo Roeder Ingo Roeder Artur C. Fassoni Ingmar Glauche Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation Frontiers in Oncology chronic myeloid leukaemia (CML) treatment free remission (TFR) dose reduction tyrosine kinase inhibitor (TKI) mathematical modelling |
| title | Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation |
| title_full | Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation |
| title_fullStr | Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation |
| title_full_unstemmed | Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation |
| title_short | Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation |
| title_sort | modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation |
| topic | chronic myeloid leukaemia (CML) treatment free remission (TFR) dose reduction tyrosine kinase inhibitor (TKI) mathematical modelling |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1028871/full |
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