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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 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.

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We are grateful to the staff for good care and nursing at our institution.

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Correspondence to Noriaki Kawano.

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The authors (Noriaki Kawano, Masatomo Miura, Taro Tochigi, Takashi Nakaike, Kiyoshi Yamashita, Koichi Mashiba, Ikuo Kikuchi) have no conflicts of interest to declare. Shinya Kimura reports that he has received speaker’s fees from Novartis Pharmaceuticals, Grants and speaker’s fees from Bristol Myers Squibb, Pfizer and Otsuka Pharmaceutical, Grants from Kyowa Hakko Kirin, Astellas Pharma, Chu-gai Pharmaceutical, Asahi Kasei Pharma, Nippon Shinyaku, Ono Pharmaceutical, Eisai Pharmaceuticals, Taiho, Pharmaceutical, Ohara pharmaceutical and Takeda outside of the submitted work. Naoto Takahashi reports that he has received Grants and speaker’s fees from Novartis Pharmaceuticals, speaker’s fees from Bristol Myers Squibb, Grants and speaker’s fees from Pfizer, Grants and speaker’s fees from Otsuka Pharmaceutical, Grants from Kyowa Hakko Kirin, Grants from Astellas Pharma, Grants from Chugai Pharmaceutical, Grants from Asahi Kasei Pharma, Grants from Ono Pharmaceutical, and Grants from Eisai Pharmaceuticals, outside of the submitted work. The remaining authors declare that they have no conflicts of interest.

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Kawano, N., Kimura, S., Miura, M. et al. Serial evaluation of the pharmacokinetics of ponatinib in patients with CML and Ph + ALL. Int J Hematol 114, 509–516 (2021).

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  • The pharmacokinetics
  • Target concentration
  • Ponatinib
  • CML
  • Ph + ALL