Annals of Hematology

, Volume 96, Issue 4, pp 549–558 | Cite as

Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion

  • Massimo BrecciaEmail author
  • Patrizia Pregno
  • Paolo Spallarossa
  • Eleonora Arboscello
  • Fabio Ciceri
  • Mauro Giorgi
  • Alberto Grossi
  • Mario Mallardo
  • Savina Nodari
  • Stefano Ottolini
  • Carla Sala
  • Giovanni Tortorella
  • Gianantonio Rosti
  • Fabrizio Pane
  • Giorgio Minotti
  • Michele Baccarani
Review Article


Ponatinib (Iclusig, ARIAD Pharmaceuticals-Incyte Co.) is a third-generation structure-guided tyrosine kinase inhibitor that is approved for treatment of Philadelphia chromosome-positive leukaemias resistant or intolerant to other inhibitors. The clinical use of ponatinib is complicated by the possible development of cardiovascular events, primarily hypertension and arterial or venous thrombotic events. The US Food and Drug Administration and the European Medicine Agency recommend that the cardiovascular profile of patients candidate for ponatinib should be carefully evaluated. For patients deemed to carry a high risk of cardiovascular events, other life-saving therapeutic options should be considered. When alternative options are not available, treatment with ponatinib is indicated but requires that haematologists and cardiologists collaborate and identify modalities of surveillance and risk mitigation in the best interest of the patient. This article reports on the expert opinion provided by a panel of Italian haematologists, cardiologists and clinical pharmacologists. It summarises suggestions that may help to improve the therapeutic index of ponatinib, primarily in the settings of chronic-phase chronic myeloid leukaemia.


Chronic myeloid leukaemia Ponatinib Cardiovascular risk Assessment Management 



Tyrosine kinase inhibitor


Vascular endothelial growth factor


Chronic myeloid leukaemia


Acute phase


Chronic phase


Blastic crisis


Philadelphia chromosome positive


Major cytogenetic response


Complete cytogenetic response


Major molecular response


Deep molecular response


Progression-free survival


Overall survival


(Serious) adverse event


Acute lymphoblastic leukaemia


Good clinical practice


European Society of Cardiology


European Society of Hypertension


Left ventricle ejection fraction


Ankle brachial index


Systematic coronary risk evaluation

CHA2DS2VASc score

Congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, stroke (doubled), vascular disease, age 65–74 years, sex category

HAS-BLED score

Hypertension, abnormal renal and liver function, stroke, bleeding, labile INRs, elderly and drugs or alcohol


International normalised ratio


New oral anticoagulants


Low molecular weight heparin


(Non)ST elevation myocardial infarction


Angiotensin II receptor blocker


Dietary approaches to stop hypertension


Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Massimo Breccia
    • 1
    Email author
  • Patrizia Pregno
    • 2
  • Paolo Spallarossa
    • 3
  • Eleonora Arboscello
    • 4
  • Fabio Ciceri
    • 5
  • Mauro Giorgi
    • 6
  • Alberto Grossi
    • 7
  • Mario Mallardo
    • 8
  • Savina Nodari
    • 9
  • Stefano Ottolini
    • 10
  • Carla Sala
    • 11
  • Giovanni Tortorella
    • 12
  • Gianantonio Rosti
    • 13
  • Fabrizio Pane
    • 14
  • Giorgio Minotti
    • 15
  • Michele Baccarani
    • 13
  1. 1.Department of Cellular Biotechnologies and HematologySapienza University-Azienda Policlinico Umberto 1RomeItaly
  2. 2.S.C. Ematologia, Dip. di Oncologia ed EmatologiaA.O.U.Città della Salute e della Scienza di TorinoRomeItaly
  3. 3.Clinica Malattie dell’Apparato CardiovascolareIRCCS AOU San MartinoGenoaItaly
  4. 4.Dipartimento di Medicina InternaUniversità degli Studi di GenovaGenoaItaly
  5. 5.Servizio Immunoematologia TrasfusionaleIRCCS San RaffaeleMilanoItaly
  6. 6.S.C. Cardiologia U., Dip. Cardiovascolare e ToracicoA.O.U.Città della Salute e della Scienza di TorinoTurinItaly
  7. 7.Ematologia Istituto Leonardo Da VinciFlorenceItaly
  8. 8.U.O.C. di Cardiologia e Riabilitazione CardiologicaOsp. San GennaroNapoliItaly
  9. 9.Dipartimento di Cardiologia e Chirurgia CardiotoracicaSpedali CiviliBresciaItaly
  10. 10.Centro Medico EcograficoPaviaItaly
  11. 11.UOC Malattie Cardiovascolari-IRCCS PoliclinicoUniversità di MilanoMilanItaly
  12. 12.CardiologiaArcispedale S. Maria NuovaReggio EmiliaItaly
  13. 13.Dipartimento di Ematologia e Oncologia “L. e A. Seràgnoli”Università di BolognaBolognaItaly
  14. 14.UO Ematologia e Trapianti di MidolloPoliclinico di NapoliItaly
  15. 15.Dip. MedicinaUniversità Campus Bio-MedicoRomeItaly

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