Five-year follow-up of OPTIC: long-term efficacy, safety, and mutation analyses of ponatinib in chronic-phase chronic myeloid leukemia from a randomized phase 2 trial

The primary analysis of the phase 2 OPTIC trial (NCT02467270) demonstrated optimal benefit:risk with response-based ponatinib dosing (45 mg once daily (QD) reduced to 15 mg QD) upon achieving ≤1% BCR::ABL1 IS in patients with tyrosine kinase inhibitor-resistant or T315I-positive chronic-phase chronic myeloid leukemia (CP-CML). Here, we report 5-year long-term outcomes. Overall, 283 patients were randomized to 45-mg, 30-mg, or 15-mg QD starting doses ( n = 94, 95, and 94, respectively), with dose reduction to 15 mg QD upon response in the 45-mg and 30-mg cohorts. At data cutoff, 61 patients remained on trial. Median follow-up time was 75–78 months. By 5 years, 60%, 41%, and 40% of patients in the 45-mg, 30-mg, and 15-mg cohorts, respectively, achieved ≤1% BCR::ABL1 IS . Five-year progression-free survival rates were 63%, 57%, and 60%, respectively, by cohort; overall survival rates exceeded 80%. In patients with a T315I mutation, 5-year rates of ≤1% BCR::ABL1 IS , PFS, and OS were highest in the 45-mg cohort. Exposure-adjusted rates of adjudicated arterial occlusive events were 4.1, 3.8, and 2.0 patients per 100 patient-years, respectively, by cohort; results were comparable in T315I-positive patients. These findings support long-term clinical benefit of response-based ponatinib dosing in third-line CP-CML, especially in patients with the T315I mutation.

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Journal
Leukemia
Published
2026-07-24
DOI
https://doi.org/10.1038/s41375-026-03009-x
Primary Topic
Chronic Myeloid Leukemia Treatments
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article
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article

Five-year follow-up of OPTIC: long-term efficacy, safety, and mutation analyses of ponatinib in chronic-phase chronic myeloid leukemia from a randomized phase 2 trial

Michael W. Deininger, Jeffrey H. Lipton, Jörge E. Cortes, Michael J. Mauro et al.
Leukemia
Chronic Myeloid Leukemia Treatments
article

Five-year follow-up of OPTIC: long-term efficacy, safety, and mutation analyses of ponatinib in chronic-phase chronic myeloid leukemia from a randomized phase 2 trial

Michael W. Deininger, Jeffrey H. Lipton, Jörge E. Cortes, Michael J. Mauro, Chris Arthur, Andreas Hochhaus, Alexander Vorog, Beatriz Moiraghi, Jane F. Apperley, Hugues de Lavallade, Elza Lomaia, Hagop M. Kantarjian, L. Evan Reddick, Carolina Pavlovsky, Philippe Rousselot, Lori Maness, Bo Chao, Niti Patel, Meliessa Hennessy, James McCloskey, Charles Chuah, Tammie Yeh, Gianantonio Rosti
article en

Abstract

The primary analysis of the phase 2 OPTIC trial (NCT02467270) demonstrated optimal benefit:risk with response-based ponatinib dosing (45 mg once daily (QD) reduced to 15 mg QD) upon achieving ≤1% BCR::ABL1 IS in patients with tyrosine kinase inhibitor-resistant or T315I-positive chronic-phase chronic myeloid leukemia (CP-CML). Here, we report 5-year long-term outcomes. Overall, 283 patients were randomized to 45-mg, 30-mg, or 15-mg QD starting doses ( n = 94, 95, and 94, respectively), with dose reduction to 15 mg QD upon response in the 45-mg and 30-mg cohorts. At data cutoff, 61 patients remained on trial. Median follow-up time was 75–78 months. By 5 years, 60%, 41%, and 40% of patients in the 45-mg, 30-mg, and 15-mg cohorts, respectively, achieved ≤1% BCR::ABL1 IS . Five-year progression-free survival rates were 63%, 57%, and 60%, respectively, by cohort; overall survival rates exceeded 80%. In patients with a T315I mutation, 5-year rates of ≤1% BCR::ABL1 IS , PFS, and OS were highest in the 45-mg cohort. Exposure-adjusted rates of adjudicated arterial occlusive events were 4.1, 3.8, and 2.0 patients per 100 patient-years, respectively, by cohort; results were comparable in T315I-positive patients. These findings support long-term clinical benefit of response-based ponatinib dosing in third-line CP-CML, especially in patients with the T315I mutation.

Leukemia
Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Université de Versailles Saint-Quentin-en-Yvelines (FR), Guy's and St Thomas' NHS Foundation Trust (GB), Singapore General Hospital (SG), University of Michigan (US), Royal North Shore Hospital (AU), Princess Margaret Cancer Centre (CA), Federal Almazov North-West Medical Research Centre (RU), Augusta University Health (US), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Hospital Ramos Mejía (AR), Duke-NUS Medical School (SG), Fundación para la Investigación, Docencia y Prevención del Cáncer (AR), Jena University Hospital (DE), Takeda (United States) (US), Hackensack Meridian Health (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Centre Hospitalier de Versailles (FR), Imperial College London (GB), University of Nebraska Medical Center (US)
Takeda Development Center Americas
Good health and well-being
Openalex Percentile: Top 9%
Chronic Myeloid Leukemia Treatments
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