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 for this work

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.

Original languageEnglish
JournalExpert Review of Clinical Pharmacology
Volume17
Issue number3
Pages (from-to)225-234
Number of pages10
ISSN1751-2433
DOIs
Publication statusPublished - Mar 2024

Keywords

  • Adult
  • Child
  • Drug Monitoring
  • Drug Resistance, Neoplasm/genetics
  • Humans
  • Imatinib Mesylate/adverse effects
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
  • Philadelphia Chromosome
  • Prospective Studies
  • Protein Kinase Inhibitors/adverse effects
  • imatinib
  • Philadelphia chromosome positive
  • tyrosine kinase inhibitors
  • Philadelphia chromosome-like
  • acute lymphoblastic leukemia
  • chronic myeloid leukemia
  • ABL-class leukemia
  • therapeutic drug monitoring

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