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Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study

Arinobu Tojo1, Taiichi Kyo2, Kazuhito Yamamoto3

  • 1The Institute of Medical Science, The University Of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. a-tojo@ims.u-tokyo.ac.jp.

International Journal of Hematology
|April 27, 2017
PubMed

Insights

Ponatinib showed efficacy in Japanese patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant to prior treatments. Safety data support a 45 mg/day starting dose for these patients.

Area of Science:

  • Hematology
  • Oncology
  • Clinical Pharmacology

Background:

  • Chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) are aggressive hematologic malignancies.
  • Resistance or intolerance to tyrosine kinase inhibitors (TKIs) poses a significant challenge in managing these diseases.
  • Ponatinib is a potent TKI investigated for patients with refractory leukemia.

Purpose of the Study:

  • To evaluate the safety and efficacy of ponatinib in Japanese patients with CML or Ph+ALL.
  • To determine the recommended starting dose of ponatinib in this patient population.
  • To assess response rates and adverse events associated with ponatinib treatment.

Main Methods:

  • Phase 1/2 study (NCT01667133) in Japanese patients with CML or Ph+ALL resistant/intolerant to prior TKIs.
  • Primary endpoints: safety of recommended dose (Phase 1), major cytogenetic response (MCyR) for CP-CML, and major hematologic response (MaHR) for advanced phase disease (Phase 2).
  • Evaluation of treatment-emergent adverse events (AEs), including hematologic and non-hematologic events, and arterial occlusive events (AOEs).

Main Results:

  • MCyR achieved/maintained by 12 months in 65% of chronic-phase CML patients.
  • MaHR achieved by 6 months in 61% of advanced phase disease patients.
  • Most common grade 3/4 AEs: thrombocytopenia (57%), hypertension (37%), neutropenia (34%), leukopenia (26%).
  • 14% of patients experienced arterial occlusive events (AOEs); no grade 5 AOEs reported.

Conclusions:

  • Ponatinib demonstrated significant efficacy in Japanese patients with CML and Ph+ALL refractory to prior TKI therapy.
  • The safety profile, including manageable AEs and AOEs, supports its use in this population.
  • A recommended starting dose of 45 mg/day for ponatinib was established based on safety and efficacy data.
Keywords:
CMLJapanese populationPh+ALLPhase 1/2Ponatinib

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