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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Long-Term Follow-Up in Patients With Chronic Myeloid Leukemia Treated With Ponatinib in a Real-World Cohort: Safety
María José Mela Osorio1, Beatriz Moiraghi2, María Victoria Osycka2
1Fundaleu - Fundación para combatir la leucemia, Buenos Aires, Argentina.
Background:
Ponatinib is a third-generation tyrosine-kinase inhibitor (TKI), indicated in patients with chronic phase (CP), accelerated phase (AP), or blast phase (BP) chronic myeloid leukemia (CML), who are resistant or intolerant to ≥2 prior TKIs, patients for whom subsequent treatment with imatinib is not appropriate, and patients who have a T315I mutation.
Patients And Methods:
We aimed to evaluate outcomes of ponatinib treatment, including safety, with focus on cardiovascular toxicity, in real-world patients from Argentina. Data from patients with CP CML treated with ponatinib was retrospectively retrieved from 2013 to 2023 in 7 centers.
Results:
Seventy-two patients were included (median age: 44 years; male: 55.5%; T315I mutation: 32%: median treatment duration: 36 months. At baseline, 57 patients (79%) had a breakpoint cluster region-Abelson (BCR::ABL1) transcript level >10% on the international reporting scale (BCR::ABL1 IS). A molecular response (MR, BCR::ABL1 (IS) <1%) was achieved at 12 months in 51.6% of evaluable patients; 57% maintained MR at last follow-up. Overall, 43% and 25% maintained major MR (MMR) or deep MR (DMR) (MR4.0-MR5.0), respectively at last follow-up. Twelve (16.6%) ponatinib-resistant patients were rescued with allogeneic hematopoietic stem cell transplantation. The estimated 2-year progression-free survival (PFS) was 84%. Ponatinib dose was reduced during treatment in 22 patients; nevertheless, MMR was maintained in 50% of these patients. Severe arterial occlusive events (AOE) were reported in 10.9% of patients after a median treatment of 5 months.
Conclusion:
CV toxicity was consistent with clinical trials and other real-world registries. Older age, hypercholesterolemia and a SCORE risk >2% were significantly associated with higher risk of AOEs. Controlling CV risk factors and reducing doses at optimal time points may help to optimize ponatinib use in daily practice.
Insights
Ponatinib effectively treats chronic myeloid leukemia (CML) in resistant patients, achieving molecular response in over half. Cardiovascular toxicity was observed, but managing risk factors and dose adjustments can optimize its use.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Ponatinib is a third-generation tyrosine-kinase inhibitor (TKI) for chronic myeloid leukemia (CML) patients resistant or intolerant to prior TKIs, or with the T315I mutation.
- It is indicated for chronic phase (CP), accelerated phase (AP), and blast phase (BP) CML.
Purpose of the Study:
- To evaluate the real-world outcomes and safety of ponatinib in Argentine patients with CP CML.
- Specific focus on cardiovascular toxicity associated with ponatinib treatment.
Main Methods:
- Retrospective data collection from 7 centers in Argentina between 2013 and 2023.
- Inclusion of patients with CP CML treated with ponatinib, analyzing safety and efficacy endpoints.
Main Results:
- Seventy-two patients were analyzed; 32% had the T315I mutation. Molecular response (MR) was achieved by 51.6% at 12 months, with 57% maintaining MR long-term.
- Major MR (MMR) and deep MR (DMR) were maintained by 43% and 25% respectively. Severe arterial occlusive events (AOE) occurred in 10.9% of patients.
- Progression-free survival (PFS) at 2 years was 84%. Dose reductions were managed in 22 patients, with 50% maintaining MMR.
Conclusions:
- Ponatinib treatment in real-world CML patients showed efficacy comparable to clinical trials.
- Cardiovascular toxicity, including AOEs, was consistent with existing data. Older age, hypercholesterolemia, and high SCORE risk were associated with increased AOE risk.
- Optimizing ponatinib use involves controlling cardiovascular risk factors and timely dose reduction.
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