Related Experiment Video

Updated: Jul 4, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Dose modification dynamics of ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) from the

Elias Jabbour1, Jane Apperley2, Jorge Cortes3

  • 1The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ejabbour@mdanderson.org.

Leukemia
|January 29, 2024
PubMed

Insights

Ponatinib effectively treats chronic myeloid leukemia (CML) resistant to other drugs. A new dose strategy in the OPTIC trial reduced cardiovascular risks compared to the PACE trial, improving patient safety.

Area of Science:

  • Oncology
  • Pharmacology
  • Hematology

Background:

  • Ponatinib is a third-generation tyrosine-kinase inhibitor (TKI) targeting BCR::ABL1, effective in resistant chronic myeloid leukemia (CML).
  • Cardiovascular toxicities, such as arterial occlusive events (AOEs), are known side effects of TKIs, including ponatinib.

Purpose of the Study:

  • To evaluate the efficacy and safety of ponatinib using a response-based dose-reduction strategy in CML patients resistant to multiple TKIs or with T315I mutation.
  • To compare the dose-response relationship and safety profile of ponatinib between the PACE and OPTIC trials.

Main Methods:

  • Analysis of outcomes for CML patients receiving 45 mg/day ponatinib in the PACE and OPTIC trials.
  • Utilized propensity score analysis to compare arterial occlusive events (AOEs) between the two trials.
  • Assessed survival rates and time to achieve BCR::ABL1IS ≤1%.

Main Results:

  • Survival rates and time to deep molecular response (BCR::ABL1IS ≤1%) were similar or improved in the OPTIC trial compared to PACE.
  • Patients with T315I mutations showed robust outcomes in both trials.
  • The OPTIC trial demonstrated a lower exposure-adjusted incidence of AOEs compared to the PACE trial.

Conclusions:

  • A response-based dosing strategy for ponatinib significantly improves treatment tolerance.
  • This novel dosing approach effectively mitigates cardiovascular risk in CML patients treated with ponatinib.
  • Ponatinib remains a crucial therapeutic option for CML, with optimized dosing enhancing its safety profile.

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