# PACE: ponatinib in Philadelphia chromosome-positive leukaemias resistant to earlier tyrosine kinase inhibitors

Source: https://onco.cc/key-papers/paper-pace-ponatinib-nejm-2013/  
OnCo record `paper-pace-ponatinib-nejm-2013` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Ponatinib produced deep responses in patients with chronic myeloid leukaemia or Philadelphia-positive acute lymphoblastic leukaemia whose disease had resisted other kinase inhibitors, including the T315I mutation that no other drug could reach.

## Summary

Phase 2 study of 449 heavily pretreated patients with chronic, accelerated or blast-phase CML or Ph-positive ALL, including 128 with the T315I gatekeeper mutation, treated with ponatinib 45 mg daily.

In chronic phase, 56 percent achieved a major cytogenetic response (70 percent of those with T315I); responses in accelerated and blast phase were lower and shorter. Arterial occlusive events emerged as the defining toxicity, later prompting dose reduction strategies.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2013
- DOI: 10.1056/NEJMoa1306494
- Authors: Cortes JE, Kim DW, Pinilla-Ibarz J, et al.
- Findings: Major cytogenetic response in 56 percent of chronic-phase patients and 70 percent of those with T315I.; Major haematological response in 55 percent of accelerated-phase and 31 percent of blast-phase or Ph-positive ALL patients.
- What it means: Ponatinib is the drug for T315I-mutated disease and for patients who have failed several inhibitors, including in accelerated and blast phase as a bridge to transplant. Cardiovascular risk must be managed actively.
- Caveats: Serious arterial thrombotic events in a substantial minority, increasing with time on treatment.; Single-arm design; response-based dose reduction (OPTIC) came later.

## Sources

- N Engl J Med 2013: https://doi.org/10.1056/NEJMoa1306494
- PubMed: https://pubmed.ncbi.nlm.nih.gov/24180494/

## Connected records

- cancers: [Chronic myeloid leukaemia, accelerated and blast phase](https://onco.cc/cancers/cml-advanced-phase/)
- drugs: [Ponatinib](https://onco.cc/drugs/ponatinib/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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