Onkológia 6/2025
Ten years of experience with ponatinib treatment in patients with chronic myelocytic leukemia
Introduction: The prognosis of patients with chronic myeloid leukemia (CML) has dramatically improved over the past two decades thanks to tyrosine kinase inhibitors (TKIs), and the survival of most patients is comparable to that of the so-called general population without CML. However, resistance to TKIs, which occurs in approximately 15–20% of patients, may worsen treatment outcomes and increase the risk of progression to advanced phases. The causes of resistance are complex. Mutations in the BCR::ABL1 kinase domain are one of these causes. In clinical practice, resistance to the first-generation TKI imatinib is most frequently encountered. A more serious problem, however, is resistance to second-generation TKIs. Ponatinib is a highly effective third-generation TKI that is active even in cases of resistance to second-generation TKIs, including the T315I mutation, which is associated with resistance to imatinib as well as to second-generation TKIs. A major challenge of effective ponatinib therapy, however, is the risk of vascular toxicity, particularly in patients with existing cardiovascular risk factors.
Patients and methods: In our study, we retrospectively analyzed a cohort of 27 patients treated with ponatinib at the Department of Hematology and Transfusiology of University Hospital in Bratislava from 2015 to 31 October 2025. The median duration of ponatinib treatment in the cohort was 24 months (1–94 months). Prior to ponatinib therapy, 7 patients had documented mutations in the BCR::ABL1 kinase domain.
Results: At the time of analysis, 23 of the 27 patients (85.19%) were alive. We documented the achievement of a deep molecular response in 17 patients (63%). At the time of analysis, 3 patients (11%) had not achieved cytogenetic remission and therefore not a deep molecular response. Two patients underwent allogeneic hematopoietic stem cell transplantation. Arterial occlusive events occurred in 3 patients. Hematologic toxicity was observed in 3 patients.
Conclusion: Our results support the use of ponatinib in the treatment of patients who are resistant to other TKIs, with caution advised in patients with cardiovascular risk factors.
Keywords: chronic myeloid leukemia, mutations, ponatinib, resistance, tyrosine kinase inhibitors
