Serial evaluation of the pharmacokinetics of ponatinib in patients with CML and Ph + ALL

Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of...

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Bibliographic Details
Published in:International journal of hematology 2021-10, Vol.114 (4), p.509-516
Main Authors: Kawano, Noriaki, Kimura, Shinya, Miura, Masatomo, Tochigi, Taro, Nakaike, Takashi, Yamashita, Kiyoshi, Mashiba, Koichi, Kikuchi, Ikuo, Takahashi, Naoto
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Case Report
Chronic myeloid leukemia
Evaluation
Hematology
Hematopoietic stem cells
Imatinib
Inhibitor drugs
Intolerance
Kinases
Leukemia
Lymphatic leukemia
Medicine
Medicine & Public Health
Myeloid leukemia
Oncology
Patients
Pharmacokinetics
Pharmacology
Philadelphia chromosome
Protein-tyrosine kinase
Remission
Side effects
Stem cell transplantation
Stem cells
Targeted cancer therapy
Transplantation
Tyrosine
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Summary:Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of the pharmacokinetics (PK) of TKIs is currently unclear. We examined the PK of the third-generation TKI ponatinib to monitor side effects and efficacy during treatments for one patient with CML-chronic phase (CP-CML) and two who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), one for CML-blastic crisis (BC-CML) and one for Ph + ALL. The patient with CP-CML was intolerant to multiple TKIs (dasatinib, nilotinib, imatinib, and bosutinib) and thus was switched to ponatinib (15 mg/day). The patients who received allo-HSCT for BC-CML and Ph + ALL received ponatinib (15 mg/day) as maintenance therapy. Notably, serial evaluation of the PK of ponatinib showed that the median trough values (ng/ml) were 17.2 (12.2–34.5), 33.1 (21.2–40.3) and 27.7 (13.6–29.9) in patients 1, 2, and 3, respectively. These values were around the target concentration (23 ng/ml). All patients are maintaining complete remission without side effects. In conclusion, serial evaluation of PK of ponatinib may yield meaningful information about its safety and efficacy.
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-021-03186-8