A dose-ranging study of the tyrosine kinase inhibitor (TKI) ponatinib revealed clinical benefit across all 3 starting doses (45 mg, 30 mg, and 15 mg) in patients with chronic phase chronic myeloid leukemia (CML-CP).

These findings, which were part of the phase 2 OPTIC study, were published in Blood.

Results from the phase 2 PACE trial showed deep and durable responses to ponatinib in patients with CML-CP. However, ponatinib treatment was associated with arterial occlusive events (AOEs) that were considered drug-related adverse events. Post hoc analyses determined AOEs to be dose-dependent.

Continue Reading

In the phase 2 OPTIC trial (ClinicalTrials.gov Identifier: NCT02467270), researchers assessed the benefit-risk profile of 3 different ponatinib starting doses to develop a novel response-based dose-reduction strategy in CML-CP.

The study enrolled 283 adults with CML-CP who were resistant or intolerant to at least 2 prior BCR-ABL1 TKIs or who had a BCR-ABL1 T315I mutation.

The patients were randomly assigned 1:1:1 to receive ponatinib at a dose of 45 mg, 30 mg, or 15 mg once daily. Patients treated with 45 mg or 30 mg reduced their dose to 15 mg upon achievement of response (BCR-ABL1IS transcript levels ≤1%).

At a median follow-up of 12 months, the response rate was 44.1% in the 45 mg cohort, 29.0% in the 30 mg cohort, and 23.1% in the 15 mg cohort.

Grade 3 to 4 treatment-emergent AOEs were reported in 5 patients in the 45 mg cohort, 5 patients in the 30 mg cohort, and 3 patients in the 15 mg cohort.

The researchers noted that, across all cohorts, these highly resistant CML-CP patients experienced a benefit from ponatinib. However, optimal benefit-risk outcomes were observed with the 45 mg starting dose of ponatinib reduced to 15 mg upon achievement of response.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Cortes J, Apperley JF, Lomaia E, et al. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: A randomized, open-label phase 2 clinical trial. Blood. Published online August 18, 2021. doi:10.1182/blood.2021012082

This article originally appeared on Cancer Therapy Advisor