Among patients with heavily pretreated chronic phase chronic myeloid leukemia (CP-CML), reaching an early cytogenetic or molecular landmark response after initiating ponatinib treatment is predictive of some clinical outcomes, according to research presented at the SOHO 2023 Annual Meeting.

Previous research and clinical data have shown that patients who receive sequential tyrosine kinase inhibitor (TKI) therapy, and patients with BCR-ABL1 mutations, are more likely to have poor clinical outcomes. Ponatinib is a BCR-ABL1 TKI that inhibits single resistance–mutation variants of BCR-ABL1, which are associated with TKI resistance.

The phase 2 PACE trial ( Identifier: NCT01207440) of ponatinib suggested promising efficacy among patients with CP-CML who displayed resistance to other TKIs, though the significance of early landmark responses was not previously known.

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For this analysis, researchers evaluated data from PACE to determine whether landmark responses at 3 months were predictive of progression-free survival, overall survival, and minimal residual disease over the long term.

PACE was a single-arm, open-label trial of ponatinib among patients with CP-CML with resistance to previous TKI therapy and a BCR-ABL1 mutation indicative of TKI resistance. The trial enrolled 270 patients with a data cutoff of February 2017.

At baseline, of 233 patients with evaluable major molecular response (MMR) data, the median age was 60 years, 55% of patients were male, and 61% of patients had received at least 3 prior TKI therapies. A total of 33 patients had experienced an MMR.

Of 267 patients with evaluable data, 55% had reached a major cytogenetic response at 12 months. At 3 months, 49%, 34%, and 14% of patients had reached a major response 1, major response 2, and MMR, respectively.

The median follow-up was 56.8 months. Analysis showed that the 4-year progression-free survival rate was improved among patients who had reached an MMR at 3 months (P =.01); this did not, however, translate into an improved overall survival benefit (P =.884).

“Patients with no 3-month early molecular response may still respond later and have favorable long-term outcome; ponatinib therapy should be continued,” the study’s presenter said.

Disclosures: This research was supported by Takeda. Please see the original reference for a full list of disclosures.


Muller MC, Cortes J, Chuah C, et al. Achieving early cytogenetic or molecular landmark response is predictive of outcomes in heavily pretreated patients with soho chronic-phase chronic myeloid leukemia treated with ponatinib in the phase 2 PACE trial: 5-year data. Presented at: the Eleventh Annual Meeting of the Society of Hematologic Oncology (SOHO); September 6-9, 2023. Abstract CML-310.