Therapeutic Drug Monitoring: A Driver to Precision Medicine for Patients with Hematological Malignancies.

Background: Targeted therapies have revolutionized the treatment of hematological malignancies, offering improved efficacy with fewer off-target effects compared to traditional chemotherapy. However, significant pharmacokinetic (PK) and pharmacodynamic (PD) variability exists among patients receiving these therapies.

Summary: Therapeutic drug monitoring (TDM) measures drug exposure and thereby helps to adjust the dose of a drug to maintain its concentration within a target range. It is frequently applied for drugs with characteristics like PK variability or narrow therapeutic window, among others, to ensure optimal therapeutic outcome while minimizing adverse effects. Many molecular targeted agents (MTAs) for malignancies, especially tyrosine kinase inhibitors, exhibit significant variability in exposure, and yet are still dosed with a "one-size-fits-all" approach. While this is partially culprit to regulatory approval requirements of MTA, it contradicts principles of targeted therapy. PK/PD variability necessitates a personalized approach to dosing in order to optimize therapeutic outcomes and minimize toxicity. TDM provides an avenue to refine dosing strategies based on individual patient characteristics.

Key messages: Through incorporation of TDM, treatment of hematological malignancies could move toward target concentration-driven dosing in clinical trials and regulatory frameworks. Establishing target concentrations for MTA requires solid exposure-response and exposure-toxicity analyses in the population of interest. To establish such reference ranges, large populational analyses are necessitated, underlining the importance of the incorporation of such endpoints into phase III trials. Economic restrictions, sample transportation logistics, turnaround times, and interpretation may hinder the application of a TDM-guided dosing approach in routine care. Ultimately, personalized TDM-guided dosing could improve patient outcomes and quality of life through minimizing toxicity.