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

Karg, Elena, Baldow, Christoph, Zerjatke, Thomas, Clark, Richard E ORCID: 0000-0002-1261-3299, Roeder, Ingo, Fassoni, Artur C and Glauche, Ingmar (2022) Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation. FRONTIERS IN ONCOLOGY, 12. 1028871-.

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Abstract

<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.

Item Type:	Article
Uncontrolled Keywords:	chronic myeloid leukaemia (CML), treatment free remission (TFR), dose reduction, tyrosine kinase inhibitor (TKI), mathematical modelling
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	15 Mar 2023 12:26
Last Modified:	15 Mar 2023 12:26
DOI:	10.3389/fonc.2022.1028871
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3169087