Management using the plasma concentration of tyrosine kinase inhibitors for the treatment of chronic myelogenous leukemia: an update

MIURA Masatomo, TAKAHASHI Naoto

doi:10.11406/rinketsu.60.1140

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Other Title

慢性骨髄性白血病治療薬チロシンキナーゼ阻害剤の血中濃度を用いた治療マネジメントupdate
マンセイコツズイセイハッケツビョウチリョウヤクチロシンキナーゼソガイザイノケッチュウノウドオモチイタチリョウマネジメント update

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Abstract

<p>Imatinib, nilotinib, dasatinib, bosutinib, and ponatinib are tyrosine kinase inhibitors used to treat chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and target concentration intervention (TCI) are novel strategies that use concentration-controlled dosing (CCD) to attain a faster and more profound clinical response in patients with CML. The target plasma trough concentration (C₀) of imatinib is 1,000 ng/ml to obtain a higher major molecular response (MMR) rate. Target nilotinib and bosutinib C₀ of 900 and 62 ng/ml, respectively, are recommended to attain a better response, whereas a target ponatinib C₀ of 21.3 ng/ml has been proposed to obtain a better response and decrease the risk of adverse events, such as vascular toxicity. Approaches for these four TKIs involve the use of TCI with specific target concentrations rather than TDM with a therapeutic range. Conversely, for dasatinib, a lower C₀ of <4.33 ng/ml is the maximum toxic concentration recommended to avoid pleural effusion. Therefore, precision dosing using CCD of TKIs for CML could maximize the clinical benefit and minimize toxicity.</p>

Journal

Rinsho Ketsueki

Rinsho Ketsueki 60 (9), 1140-1147, 2019

The Japanese Society of Hematology

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