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

M. Breccia, P Pregno, P. Spallarossa, Eleonora Arboscello, F. Ciceri, M. Giorgi, A. Grossi, M. Mallardo, Savina Nodari, S. Ottolini, C. Sala, G. Tortorella, G. Rosti, F. Pane, Giorgio Minotti, M. Baccarani

Research output: Contribution to journalArticle

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. © 2016, Springer-Verlag Berlin Heidelberg.
Original languageEnglish
JournalAnnals of Hematology
Early online dateSep 30 2016
DOIs
Publication statusPublished - 2016

Fingerprint

Risk Management
Expert Testimony
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Berlin
United States Food and Drug Administration
Therapeutics
Protein-Tyrosine Kinases
ponatinib
Leukemia
Medicine
Hypertension
Pharmaceutical Preparations

Keywords

  • Assessment
  • Cardiovascular risk
  • Chronic myeloid leukaemia
  • Management
  • Ponatinib

Cite this

Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion. / Breccia, M.; Pregno, P; Spallarossa, P.; Arboscello, Eleonora; Ciceri, F.; Giorgi, M.; Grossi, A.; Mallardo, M.; Nodari, Savina; Ottolini, S.; Sala, C.; Tortorella, G.; Rosti, G.; Pane, F.; Minotti, Giorgio; Baccarani, M.

In: Annals of Hematology, 2016.

Research output: Contribution to journalArticle

Breccia, M, Pregno, P, Spallarossa, P, Arboscello, E, Ciceri, F, Giorgi, M, Grossi, A, Mallardo, M, Nodari, S, Ottolini, S, Sala, C, Tortorella, G, Rosti, G, Pane, F, Minotti, G & Baccarani, M 2016, 'Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion', Annals of Hematology. https://doi.org/10.1007/s00277-016-2820-x
Breccia, M. ; Pregno, P ; Spallarossa, P. ; Arboscello, Eleonora ; Ciceri, F. ; Giorgi, M. ; Grossi, A. ; Mallardo, M. ; Nodari, Savina ; Ottolini, S. ; Sala, C. ; Tortorella, G. ; Rosti, G. ; Pane, F. ; Minotti, Giorgio ; Baccarani, M. / Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion. In: Annals of Hematology. 2016.
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title = "Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion",
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. {\circledC} 2016, Springer-Verlag Berlin Heidelberg.",
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author = "M. Breccia and P Pregno and P. Spallarossa and Eleonora Arboscello and F. Ciceri and M. Giorgi and A. Grossi and M. Mallardo and Savina Nodari and S. Ottolini and C. Sala and G. Tortorella and G. Rosti and F. Pane and Giorgio Minotti and M. Baccarani",
note = "Export Date: 21 March 2017 CODEN: ANHEE Correspondence Address: Breccia, M.; Department of Cellular Biotechnologies and Hematology, Sapienza University-Azienda Policlinico Umberto 1Italy; email: breccia@bce.uniroma1.it References: Hoy, S.M., Ponatinib: a review of its use in adults with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia (2014) Drugs, 74, pp. 793-806. , COI: 1:CAS:528:DC{\%}2BC2cXnslOhtLk{\%}3D, PID: 24807266; Zhou, T., Commodore, L., Huang, W.S., Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance (2011) Chem Biol Drug Des, 77, pp. 1-11. , COI: 1:CAS:528:DC{\%}2BC3MXivF2ktr8{\%}3D, PID: 21118377; O’Hare, T., Shakespeare, W.C., Zhu, X., AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance (2009) Cancer Cell, 16, pp. 401-412. , PID: 19878872; Cortes, J.E., Kantarjian, H., Shah, N.P., Ponatinib in refractory Philadelphia chromosome-positive leukemias (2012) N Engl J Med, 367, pp. 2075-2088. , COI: 1:CAS:528:DC{\%}2BC38XhslyltrvJ, PID: 23190221; Talpaz, M., Cortes, J.E., Kantarjian, H., Long-term follow-up of a phase 1 study of ponatinib in patients with chronic phase chronic myeloid leukemia (2014) Blood, 124, p. 4558A; Cortes, J.E., Kim, D.W., Pinilla-Ibarz, J., A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias (2013) N Engl J Med, 369, pp. 1783-1796. , COI: 1:CAS:528:DC{\%}2BC3sXhslGhtLfK, PID: 24180494; Hochhaus, A., Cortes, J.E., Kim, D.-W., Efficacy and safety of ponatinib in CP-CML patients by number of prior tyrosine kinase inhibitors: 4-year follow-up of the phase 2 PACE trial (2015) Blood, 126, p. 4025A; Gainor, J.F., Chabner, B.A., Ponatinib: accelerated disapproval (2015) Oncologist, 20, pp. 847-848. , PID: 26173838; Lipton, J., Chuah, C., Guerci-Bresler, A., EPIC: a phase 3 trial of ponatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CP-CML) (2014) Blood, 124, p. 519A; Kantarjian, H.M., Kim, D.-W., Pinilla-Ibarz, J., Ponatinib in patients (pts) with Philadelphia chromosome-positive (Ph+) leukemias resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation: longer-term follow up of the PACE trial (2014) J Clin Oncol, 32 (5S), p. 7081A; Cortes, J.E., Kim, D.-W., Pinilla-Ibarz, J., Long-term follow-up of ponatinib efficacy and safety in the phase 2 PACE trial (2014) Blood, 124, p. 3135A; Mauro, M.J., Talpaz, M., Cortes, J.E., Four-year minimum follow-up for patients with chronic-phase chronic myeloid leukemia continuing to receive ponatinib in a phase 1 trial. European School of Haematology (2015) 17th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy (abstract); Huang, W.S., Metcalf, C.A., Sundaramoorthi, R., Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl) phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant (2010) J Med Chem, 53, pp. 4701-4719. , COI: 1:CAS:528:DC{\%}2BC3cXmslels7s{\%}3D, PID: 20513156; Perk, J., De Backer, G., Gohlke, H., European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and other Societies on Cardiovascular Disease Prevention in Clinical Practice (2012) Eur Heart J, 33, pp. 1635-1701. , COI: 1:CAS:528:DC{\%}2BC38XhtVeitr3P, PID: 22555213; Mancia, G., Fagard, R., Narkiewicz, K., 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) (2013) Eur Heart J, 34, pp. 2159-2219. , PID: 23771844; Leng, G.C., Fowkes, F.G., The Edinburgh Claudication Questionnaire: an improved version of the WHO/Rose Questionnaire for use in epidemiological surveys (1992) Clin Epidemiol, 45, pp. 1101-1109. , COI: 1:STN:280:DyaK3s7hsFOntQ{\%}3D{\%}3D; Heiblig, M., Sobh, M., Nicolini, F.E., Subcutaneous omocetaxine mepesuccinate in patients with chronic myeloid leukemia in tyrosine kinase inhibitor-resistant patients: review and perspectives (2014) Leuk Res, 38, pp. 1145-1153. , COI: 1:CAS:528:DC{\%}2BC2cXpvFGisb8{\%}3D, PID: 24906663; Tendera, M., Aboyans, V., ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC) (2011) Eur Heart J, 32, pp. 2851-2906; Conroy, R.M., Py{\"o}r{\"a}l{\"a}, K., Fitzgerald, A.P., Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project (2003) Eur Heart J, 24, pp. 987-1003. , COI: 1:STN:280:DC{\%}2BD3s3mtFGnuw{\%}3D{\%}3D, PID: 12788299; Lip, G.Y., Nieuwlaat, R., Pisters, R., Lane, D.A., Crijns, H.J., Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation (2010) Chest, 137, pp. 263-272. , PID: 19762550; Camm, A.J., Kirchhof, P., Lip, G.Y., Schotten, U., Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC) (2010) Eur Heart J, 31, pp. 2369-2429; Pisters, R., Lane, D.A., Nieuwlaat, R., de Vos, C.B., Crijns, H.J., Lip, G.Y., A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey (2010) Chest, 138, pp. 1093-1100. , PID: 20299623; Heidbuchel, H., Verhamme, P., Alings, M., Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation (2015) Europace, 17, pp. 1467-1507. , PID: 26324838; (2014) Annex 1, summary of product characteristics, pp. 1-60; Windecker, S., Kolh, P., 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) (2014) Eur Heart J, 35, pp. 2541-2619; Lip, G.Y., Don’t add aspirin for associated stable vascular disease in a patient with atrial fibrillation receiving anticoagulation (2008) BMJ, 336, pp. 614-615. , PID: 18340078; Konstantinides, S.V., Torbicki, A., Agnelli, G., 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism (2014) Eur Heart J, 35, pp. 3033-3069. , COI: 1:CAS:528:DC{\%}2BC28XitVyhtbzF, PID: 25173341; Loren, C.P., Aslan, J.E., Rigg, R.A., The BCR-ABL inhibitor ponatinib inhibits platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear (2015) Thromb Res, 135, pp. 155-160. , COI: 1:CAS:528:DC{\%}2BC2cXhvF2mtr3K, PID: 25527332; Neelakantan, P., Marin, D., Laffan, M., Platelet dysfunction associated with ponatinib, a new pan BCR-ABL inhibitor with efficacy for chronic myeloid leukemia resistant to multiple tyrosine kinase inhibitor therapy (2012) Haematologica, 97, p. 1444. , PID: 22532521; Nazha, A., Romo, C.G., Kantarjian, H., Cortes, J., The clinical impact of ponatinib on the risk of bleeding in patients with chronic myeloid leukemia (2013) Haematologica, 98. , PID: 24091930; Diagnosis and classification of diabetes mellitus (2012) Diabetes Care, 35, pp. S64-S71; Ryd{\'e}n, L., Grant, P.J., ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD) (2013) Eur Heart J, 34, pp. 3035-3087; Nicolini, F.E., Cortes, J.E., Kim, D.-W., Dose intensity on response to ponatinib in patients with Philadelphia chromosome-positive leukemias (2014) 19th Congress of the European Hematology Association 894A; Knickerbocker, R., Dorer, D., Haluska, F., Impact of dose intensity of ponatinib on selected adverse events: multivariate analysis from a pooled population of clinical trial patients (2014) Blood, 124, p. 4546A; Steegmann, J.L., Baccarani, M., Breccia, M., European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia (2016) Leukemia; Valent, P., Hadzijusufovic, E., Schernthaner, G.-H., Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors (2015) Blood, 125, pp. 901-906. , COI: 1:CAS:528:DC{\%}2BC2MXislGgs7g{\%}3D, PID: 25525119; Moslehi, J.J., Deininger, M., Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia (2015) J Clin Oncol, 33, pp. 4210-4218. , COI: 1:CAS:528:DC{\%}2BC28XmvVyntrY{\%}3D, PID: 26371140; Gozgit, J.M., Song, Y., Baker, T., Comparative analysis of BCR-ABL and VEGFR2 inhibitory activities of ponatinib, PF-114, and axitinib (2015) 25th Meeting of the European School of Hematology, 1075A; Rivera, V.M., Pritchard, J.R., Gonzalvez, F., Comparative TKI profiling analyses to explore potential mechanisms of ponatinib-associated arterial adverse events (2014) Blood, 124, p. 1784A; Saneei, P., Salehi-Abargouei, A., Esmaillzadeh, A., Azadbakht, L., Influence of dietary approaches to stop hypertension (DASH) diet on blood pressure: a systematic review and meta-analysis on randomized controlled trials (2014) Nutr Metab Cardiovasc Dis, 24, pp. 1253-1261. , COI: 1:STN:280:DC{\%}2BC2M{\%}2FksVCrsg{\%}3D{\%}3D, PID: 25149893",
year = "2016",
doi = "10.1007/s00277-016-2820-x",
language = "English",
journal = "Annals of Hematology",
issn = "0939-5555",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion

AU - Breccia, M.

AU - Pregno, P

AU - Spallarossa, P.

AU - Arboscello, Eleonora

AU - Ciceri, F.

AU - Giorgi, M.

AU - Grossi, A.

AU - Mallardo, M.

AU - Nodari, Savina

AU - Ottolini, S.

AU - Sala, C.

AU - Tortorella, G.

AU - Rosti, G.

AU - Pane, F.

AU - Minotti, Giorgio

AU - Baccarani, M.

N1 - Export Date: 21 March 2017 CODEN: ANHEE Correspondence Address: Breccia, M.; Department of Cellular Biotechnologies and Hematology, Sapienza University-Azienda Policlinico Umberto 1Italy; email: breccia@bce.uniroma1.it References: Hoy, S.M., Ponatinib: a review of its use in adults with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia (2014) Drugs, 74, pp. 793-806. , COI: 1:CAS:528:DC%2BC2cXnslOhtLk%3D, PID: 24807266; Zhou, T., Commodore, L., Huang, W.S., Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance (2011) Chem Biol Drug Des, 77, pp. 1-11. , COI: 1:CAS:528:DC%2BC3MXivF2ktr8%3D, PID: 21118377; O’Hare, T., Shakespeare, W.C., Zhu, X., AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance (2009) Cancer Cell, 16, pp. 401-412. , PID: 19878872; Cortes, J.E., Kantarjian, H., Shah, N.P., Ponatinib in refractory Philadelphia chromosome-positive leukemias (2012) N Engl J Med, 367, pp. 2075-2088. , COI: 1:CAS:528:DC%2BC38XhslyltrvJ, PID: 23190221; Talpaz, M., Cortes, J.E., Kantarjian, H., Long-term follow-up of a phase 1 study of ponatinib in patients with chronic phase chronic myeloid leukemia (2014) Blood, 124, p. 4558A; Cortes, J.E., Kim, D.W., Pinilla-Ibarz, J., A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias (2013) N Engl J Med, 369, pp. 1783-1796. , COI: 1:CAS:528:DC%2BC3sXhslGhtLfK, PID: 24180494; Hochhaus, A., Cortes, J.E., Kim, D.-W., Efficacy and safety of ponatinib in CP-CML patients by number of prior tyrosine kinase inhibitors: 4-year follow-up of the phase 2 PACE trial (2015) Blood, 126, p. 4025A; Gainor, J.F., Chabner, B.A., Ponatinib: accelerated disapproval (2015) Oncologist, 20, pp. 847-848. , PID: 26173838; Lipton, J., Chuah, C., Guerci-Bresler, A., EPIC: a phase 3 trial of ponatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CP-CML) (2014) Blood, 124, p. 519A; Kantarjian, H.M., Kim, D.-W., Pinilla-Ibarz, J., Ponatinib in patients (pts) with Philadelphia chromosome-positive (Ph+) leukemias resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation: longer-term follow up of the PACE trial (2014) J Clin Oncol, 32 (5S), p. 7081A; Cortes, J.E., Kim, D.-W., Pinilla-Ibarz, J., Long-term follow-up of ponatinib efficacy and safety in the phase 2 PACE trial (2014) Blood, 124, p. 3135A; Mauro, M.J., Talpaz, M., Cortes, J.E., Four-year minimum follow-up for patients with chronic-phase chronic myeloid leukemia continuing to receive ponatinib in a phase 1 trial. European School of Haematology (2015) 17th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy (abstract); Huang, W.S., Metcalf, C.A., Sundaramoorthi, R., Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl) phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant (2010) J Med Chem, 53, pp. 4701-4719. , COI: 1:CAS:528:DC%2BC3cXmslels7s%3D, PID: 20513156; Perk, J., De Backer, G., Gohlke, H., European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and other Societies on Cardiovascular Disease Prevention in Clinical Practice (2012) Eur Heart J, 33, pp. 1635-1701. , COI: 1:CAS:528:DC%2BC38XhtVeitr3P, PID: 22555213; Mancia, G., Fagard, R., Narkiewicz, K., 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) (2013) Eur Heart J, 34, pp. 2159-2219. , PID: 23771844; Leng, G.C., Fowkes, F.G., The Edinburgh Claudication Questionnaire: an improved version of the WHO/Rose Questionnaire for use in epidemiological surveys (1992) Clin Epidemiol, 45, pp. 1101-1109. , COI: 1:STN:280:DyaK3s7hsFOntQ%3D%3D; Heiblig, M., Sobh, M., Nicolini, F.E., Subcutaneous omocetaxine mepesuccinate in patients with chronic myeloid leukemia in tyrosine kinase inhibitor-resistant patients: review and perspectives (2014) Leuk Res, 38, pp. 1145-1153. , COI: 1:CAS:528:DC%2BC2cXpvFGisb8%3D, PID: 24906663; Tendera, M., Aboyans, V., ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC) (2011) Eur Heart J, 32, pp. 2851-2906; Conroy, R.M., Pyörälä, K., Fitzgerald, A.P., Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project (2003) Eur Heart J, 24, pp. 987-1003. , COI: 1:STN:280:DC%2BD3s3mtFGnuw%3D%3D, PID: 12788299; Lip, G.Y., Nieuwlaat, R., Pisters, R., Lane, D.A., Crijns, H.J., Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation (2010) Chest, 137, pp. 263-272. , PID: 19762550; Camm, A.J., Kirchhof, P., Lip, G.Y., Schotten, U., Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC) (2010) Eur Heart J, 31, pp. 2369-2429; Pisters, R., Lane, D.A., Nieuwlaat, R., de Vos, C.B., Crijns, H.J., Lip, G.Y., A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey (2010) Chest, 138, pp. 1093-1100. , PID: 20299623; Heidbuchel, H., Verhamme, P., Alings, M., Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation (2015) Europace, 17, pp. 1467-1507. , PID: 26324838; (2014) Annex 1, summary of product characteristics, pp. 1-60; Windecker, S., Kolh, P., 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) (2014) Eur Heart J, 35, pp. 2541-2619; Lip, G.Y., Don’t add aspirin for associated stable vascular disease in a patient with atrial fibrillation receiving anticoagulation (2008) BMJ, 336, pp. 614-615. , PID: 18340078; Konstantinides, S.V., Torbicki, A., Agnelli, G., 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism (2014) Eur Heart J, 35, pp. 3033-3069. , COI: 1:CAS:528:DC%2BC28XitVyhtbzF, PID: 25173341; Loren, C.P., Aslan, J.E., Rigg, R.A., The BCR-ABL inhibitor ponatinib inhibits platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear (2015) Thromb Res, 135, pp. 155-160. , COI: 1:CAS:528:DC%2BC2cXhvF2mtr3K, PID: 25527332; Neelakantan, P., Marin, D., Laffan, M., Platelet dysfunction associated with ponatinib, a new pan BCR-ABL inhibitor with efficacy for chronic myeloid leukemia resistant to multiple tyrosine kinase inhibitor therapy (2012) Haematologica, 97, p. 1444. , PID: 22532521; Nazha, A., Romo, C.G., Kantarjian, H., Cortes, J., The clinical impact of ponatinib on the risk of bleeding in patients with chronic myeloid leukemia (2013) Haematologica, 98. , PID: 24091930; Diagnosis and classification of diabetes mellitus (2012) Diabetes Care, 35, pp. S64-S71; Rydén, L., Grant, P.J., ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD) (2013) Eur Heart J, 34, pp. 3035-3087; Nicolini, F.E., Cortes, J.E., Kim, D.-W., Dose intensity on response to ponatinib in patients with Philadelphia chromosome-positive leukemias (2014) 19th Congress of the European Hematology Association 894A; Knickerbocker, R., Dorer, D., Haluska, F., Impact of dose intensity of ponatinib on selected adverse events: multivariate analysis from a pooled population of clinical trial patients (2014) Blood, 124, p. 4546A; Steegmann, J.L., Baccarani, M., Breccia, M., European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia (2016) Leukemia; Valent, P., Hadzijusufovic, E., Schernthaner, G.-H., Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors (2015) Blood, 125, pp. 901-906. , COI: 1:CAS:528:DC%2BC2MXislGgs7g%3D, PID: 25525119; Moslehi, J.J., Deininger, M., Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia (2015) J Clin Oncol, 33, pp. 4210-4218. , COI: 1:CAS:528:DC%2BC28XmvVyntrY%3D, PID: 26371140; Gozgit, J.M., Song, Y., Baker, T., Comparative analysis of BCR-ABL and VEGFR2 inhibitory activities of ponatinib, PF-114, and axitinib (2015) 25th Meeting of the European School of Hematology, 1075A; Rivera, V.M., Pritchard, J.R., Gonzalvez, F., Comparative TKI profiling analyses to explore potential mechanisms of ponatinib-associated arterial adverse events (2014) Blood, 124, p. 1784A; Saneei, P., Salehi-Abargouei, A., Esmaillzadeh, A., Azadbakht, L., Influence of dietary approaches to stop hypertension (DASH) diet on blood pressure: a systematic review and meta-analysis on randomized controlled trials (2014) Nutr Metab Cardiovasc Dis, 24, pp. 1253-1261. , COI: 1:STN:280:DC%2BC2M%2FksVCrsg%3D%3D, PID: 25149893

PY - 2016

Y1 - 2016

N2 - 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. © 2016, Springer-Verlag Berlin Heidelberg.

AB - 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. © 2016, Springer-Verlag Berlin Heidelberg.

KW - Assessment

KW - Cardiovascular risk

KW - Chronic myeloid leukaemia

KW - Management

KW - Ponatinib

U2 - 10.1007/s00277-016-2820-x

DO - 10.1007/s00277-016-2820-x

M3 - Article

JO - Annals of Hematology

JF - Annals of Hematology

SN - 0939-5555

ER -