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

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Abstract

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.

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Abbreviations

TKI:

Tyrosine kinase inhibitor

VEGF:

Vascular endothelial growth factor

CML:

Chronic myeloid leukaemia

AP:

Acute phase

CP:

Chronic phase

BC:

Blastic crisis

Ph+ :

Philadelphia chromosome positive

MCyR:

Major cytogenetic response

CCyR:

Complete cytogenetic response

MMR:

Major molecular response

MR4.5:

Deep molecular response

PFS:

Progression-free survival

OS:

Overall survival

(S)AE:

(Serious) adverse event

ALL:

Acute lymphoblastic leukaemia

GCP:

Good clinical practice

ESC:

European Society of Cardiology

ESH:

European Society of Hypertension

LVEF:

Left ventricle ejection fraction

ABI:

Ankle brachial index

SCORE:

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

INR:

International normalised ratio

NOA:

New oral anticoagulants

LMWH:

Low molecular weight heparin

(N)STEMI:

(Non)ST elevation myocardial infarction

ARB:

Angiotensin II receptor blocker

DASH:

Dietary approaches to stop hypertension

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Author information

Authors and Affiliations

  1. Department of Cellular Biotechnologies and Hematology, Sapienza University-Azienda Policlinico Umberto 1, Rome, Italy

    Massimo Breccia

  2. S.C. Ematologia, Dip. di Oncologia ed Ematologia, A.O.U.Città della Salute e della Scienza di Torino, Rome, Italy

    Patrizia Pregno

  3. Clinica Malattie dell’Apparato Cardiovascolare, IRCCS AOU San Martino, Genoa, Italy

    Paolo Spallarossa

  4. Dipartimento di Medicina Interna, Università degli Studi di Genova, Genoa, Italy

    Eleonora Arboscello

  5. Servizio Immunoematologia Trasfusionale, IRCCS San Raffaele, Milano, Italy

    Fabio Ciceri

  6. S.C. Cardiologia U., Dip. Cardiovascolare e Toracico, A.O.U.Città della Salute e della Scienza di Torino, Turin, Italy

    Mauro Giorgi

  7. Ematologia Istituto Leonardo Da Vinci, Florence, Italy

    Alberto Grossi

  8. U.O.C. di Cardiologia e Riabilitazione Cardiologica, Osp. San Gennaro, Napoli, Italy

    Mario Mallardo

  9. Dipartimento di Cardiologia e Chirurgia Cardiotoracica, Spedali Civili, Brescia, Italy

    Savina Nodari

  10. Centro Medico Ecografico, Pavia, Italy

    Stefano Ottolini

  11. UOC Malattie Cardiovascolari-IRCCS Policlinico, Università di Milano, Milan, Italy

    Carla Sala

  12. Cardiologia, Arcispedale S. Maria Nuova, Reggio Emilia, Italy

    Giovanni Tortorella

  13. Dipartimento di Ematologia e Oncologia “L. e A. Seràgnoli”, Università di Bologna, Bologna, Italy

    Gianantonio Rosti & Michele Baccarani

  14. UO Ematologia e Trapianti di Midollo, Policlinico di Napoli, Italy

    Fabrizio Pane

  15. Dip. Medicina, Università Campus Bio-Medico, Rome, Italy

    Giorgio Minotti

Authors
  1. Massimo Breccia
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  2. Patrizia Pregno
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  4. Eleonora Arboscello
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  5. Fabio Ciceri
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  9. Savina Nodari
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  10. Stefano Ottolini
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  11. Carla Sala
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  13. Gianantonio Rosti
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  14. Fabrizio Pane
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  15. Giorgio Minotti
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  16. Michele Baccarani
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Corresponding author

Correspondence to Massimo Breccia.

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The authors declare that they have no conflict of interest.

Additional information

Massimo Breccia, Patrizia Pregno, Paolo Spallarossa, Giorgio Minotti and Michele Baccarani: writing committee

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Breccia, M., Pregno, P., Spallarossa, P. et al. Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion. Ann Hematol 96, 549–558 (2017). https://doi.org/10.1007/s00277-016-2820-x

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  • DOI: https://doi.org/10.1007/s00277-016-2820-x

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