Therapeutic drug monitoring of imatinib - how far are we in the leukemia setting?

Anna Sofie Buhl Rasmussen, Christen Lykkegaard Andersen, Allan Weimann, Tianwu Yang, Camille Tron, Virginie Gandemer, Kim Dalhoff, Cecilie Utke Rank, Kjeld Schmiegelow*

*Corresponding author af dette arbejde

Abstract

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have revolutionized survival rates of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) and replaced hematopoietic stem cell transplantation (hSCT) as the key treatment option for these patients. More recently, the so-called Philadelphia chromosome-like (Ph-like) ALL has similarly benefitted from TKIs. However, many patients shift from the first generation TKI, imatinib, due to treatment-related toxicities or lack of treatment efficacy. A more personalized approach to TKI treatment could counteract these challenges and potentially be more cost-effective. Therapeutic drug monitoring (TDM) has led to higher response rates and less treatment-related toxicity in adult CML but is rarely used in ALL or in childhood CML.

AREAS COVERED: This review summarizes different antileukemic treatment indications for TKIs with focus on imatinib and its pharmacokinetic/-dynamic properties as well as opportunities and pitfalls of TDM for imatinib treatment in relation to pharmacogenetics and co-medication for pediatric and adult Ph+/Ph-like leukemias.

EXPERT OPINION: TDM of imatinib adds value to standard monitoring of ABL-class leukemia by uncovering non-adherence and potentially mitigating adverse effects. Clinically implementable pharmacokinetic/-dynamic models adjusted for relevant pharmacogenetics could improve individual dosing. Prospective trials of TDM-based treatments, including both children and adults, are needed.

OriginalsprogEngelsk
TidsskriftExpert Review of Clinical Pharmacology
Vol/bind17
Udgave nummer3
Sider (fra-til)225-234
Antal sider10
ISSN1751-2433
DOI
StatusUdgivet - mar. 2024

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