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Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

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Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

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Abbreviations

CML:

chronic myeloid leukemia

MMR:

major molecular response

VEGF:

vascular endothelial growth factor

TKI:

tyrosine kinase inhibitor

CHF:

congestive heart failure

PAH:

pulmonary arterial hypertension

TEAEs:

treatment-emergent adverse events

PAD:

peripheral artery disease

MI:

myocardial infarction

CAD:

coronary artery disease

IMT:

intima-media thickness

CTRCD:

cancer therapeutics-related cardiac dysfunction

CMR:

cardiac magnetic resonance

GLS:

global longitudinal strain

CCyR:

complete cytogenetic response

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Authors and Affiliations

  1. Ospedali Riuniti University Hospital, Foggia, Italy

    Grazia Casavecchia, Matteo Gravina & Silvana Capalbo

  2. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy

    Maurizio Galderisi

  3. Biomedic Department of Internal Medicine and Specialities (DIBIMIS), University of Palermo, Palermo, Italy

    Giuseppina Novo

  4. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy

    Ciro Santoro

  5. Echocardiography Laboratory, San Raffaele University Hospital IRRCS Milan, Milan, Italy

    Eustachio Agricola

  6. Department of Medical & Surgical Sciences, University of Foggia, Foggia, Italy

    Stefano Zicchino & Natale Daniele Brunetti

  7. Department of Cardiovascular Diseases, University of Siena, Siena, Italy

    Matteo Cameli & Francesca Maria Righini

  8. San Paolo Hospital, Bari, Italy

    Luisa De Gennaro

  9. General surgery and Medical-Surgery Specialities, University of Catania, Catania, Italy

    Ines Monte

  10. Department of Translational Medical Sciences, Federico II University, Naples, Italy

    Carlo Gabriele Tocchetti

  11. Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy

    Cristian Cadeddu & Giuseppe Mercuro

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  1. Grazia Casavecchia
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  2. Maurizio Galderisi
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Correspondence to Natale Daniele Brunetti.

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Casavecchia, G., Galderisi, M., Novo, G. et al. Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib. Heart Fail Rev 25, 447–456 (2020). https://doi.org/10.1007/s10741-020-09926-y

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