Therapeutic drug monitoring in acute lymphoblastic leukemia–a deep dive into pharmacokinetics, -dynamics, and -genetics of antileukemic drugs

Introduction: Therapeutic drug monitoring (TDM) is important to optimize drug exposure and minimize toxicity for the individual patient. Areas covered: This narrative review covers the pharmacokinetics (PK), -dynamics (PD) and -genetics of classic chemotherapeutic drugs used in frontline therapy for acute lymphoblastic leukemia (ALL), including anthracyclines, asparaginase, busulfan, cyclophosphamide, cytarabine, glucocorticoids, methotrexate, nelarabine, thiopurines, tyrosine kinase inhibitors, and vincristine. Furthermore, novel immunotherapies including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T-cells that are rapidly moving into frontline therapy are addressed. This review focuses on TDM already used in clinical practice as well as the unused potential and feasibility of TDM. Finally, important factors affecting PK/PD such as obesity and transition to adolescence and young adulthood are discussed. Expert opinion: Investigation of TDM as standard of care for antileukemic agents is highly warranted to personalize curative yet toxic anticancer regimens within frontline ALL treatment. Some of the drugs have been used in ALL treatment regimens for decades, but a wide range of new compounds are being introduced, some like blinatumomab reaching standard-of-care designation. Not least, optimized drug efficacy and reduction of the risk of serious toxicities may render TDM implementation cost-effective.