Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation.

Autor:	Karg E; Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Baldow C; Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Zerjatke T; Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Clark RE; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom., Roeder I; Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.; National 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, Germany., Fassoni AC; Instituto de Matemática e Computação, Universidade Federal de Itajubá (UNIFEI), Itajubá, Brazil., Glauche I; Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Dec 06; Vol. 12, pp. 1028871. Date of Electronic Publication: 2022 Dec 06 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.1028871
Abstrakt:	Introduction: Discontinuation 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. Methods: Here, 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. Results: Our 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. Discussion: Our 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. Competing Interests: RC is a consultant for Pfizer. IR reports receiving a commercial research grant from Bristol-Myers Squibb and has received speakers bureau honoraria from Bristol-Myers Squibb and Janssen-Cilag. IG reports receiving a commercial research grant from Bristol-Myers Squibb and from GlaxoSmithKline. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Karg, Baldow, Zerjatke, Clark, Roeder, Fassoni and Glauche.)
Databáze:	MEDLINE
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