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Efficacy and safety of ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a case series from a single institute

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Abstract

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is an aggressive leukemia that occurs in 20–40% of adult patients. Ph + ALL is caused by the Philadelphia chromosome (Ph), which consists of a t(9;22)(q34;q11) reciprocal translocation leading to the formation of a BCR-ABL1 fusion gene. The disease is treated with targeted therapy comprising ABL1 tyrosine kinase inhibitors (TKIs). Ponatinib is a third generation TKI that demonstrates higher binding affinity for ABL1 than first/second generation TKIs. Although intensive combined immunotherapy with ponatinib greatly improves the prognosis of Ph + ALL, the safety and efficacy profiles of ponatinib in Japanese patients are unclear. This retrospective study investigated five cases of Ph + ALL at a single institute to evaluate safety and efficacy profiles. Three patients achieved a deep molecular response (DMR) following combined intensive treatment with ponatinib as induction chemotherapy. Four patients received consolidative allogenic stem cell transplantation (allo-SCT) during their first complete response. Three of the four experienced early relapse within 100 days; they subsequently received ponatinib, and one of the three achieved a DMR. No patient experienced severe cardiovascular events. This case series suggests that ponatinib at a concentration of least 30 mg exhibits anti-leukemia effects in Japanese patients with Ph + ALL.

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Funding

This work was supported by research grants from the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (19K17860, to H.U.), the Okinaka Memorial Institute for Medical Research (to H.U.), and the Shinnihon Foundation of Advanced Medical Treatment Research (to H.U.).

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Authors and Affiliations

  1. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Keisuke Kidoguchi, Hiroshi Ureshino, Haruna Kizuka-Sano, Kyosuke Yamaguchi, Hiroo Katsuya, Yasushi Kubota, Toshihiko Ando & Shinya Kimura

  2. Department of Transfusion Medicine, Saga University Hospital, Saga, Japan

    Yasushi Kubota

  3. Department of Pharmacy, Akita University Hospital, Akita, Japan

    Masatomo Miura

  4. Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan

    Naoto Takahashi

Authors
  1. Keisuke Kidoguchi
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  2. Hiroshi Ureshino
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  3. Haruna Kizuka-Sano
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  4. Kyosuke Yamaguchi
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  5. Hiroo Katsuya
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  6. Yasushi Kubota
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  7. Toshihiko Ando
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  8. Masatomo Miura
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  9. Naoto Takahashi
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  10. Shinya Kimura
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Corresponding author

Correspondence to Hiroshi Ureshino.

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Conflict of interest

SK has received research grants from Chugai Pharmaceutical, Daiichi-Sankyo, Astellas, TAIHO PHARMA, Novartis, Takeda, Asahi Kasei Pharma, and Ohara Pharmaceutical, and a speaker honorarium from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceutical.

Ethical approval

All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee, and in accordance with the 1964 Helsinki Declaration and its later amendments (or comparable ethical standards).

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Appendix

Appendix

The study was approved by the Ethics Committees of Saga University Hospital.

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Cite this article

Kidoguchi, K., Ureshino, H., Kizuka-Sano, H. et al. Efficacy and safety of ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a case series from a single institute. Int J Hematol 114, 199–204 (2021). https://doi.org/10.1007/s12185-021-03156-0

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  • DOI: https://doi.org/10.1007/s12185-021-03156-0

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