Advertisement

Annals of Hematology

, Volume 98, Issue 8, pp 1885–1890 | Cite as

Incidence and evaluation of predisposition to cardiovascular toxicity in chronic myeloid leukemia patients treated with bosutinib in the real-life practice

  • Giovanni CaocciEmail author
  • Olga Mulas
  • Elisabetta Abruzzese
  • Alessandra Iurlo
  • Mario Annunziata
  • Ester Maria Orlandi
  • Sara Galimberti
  • Gianni Binotto
  • Nicola Sgherza
  • Luigia Luciano
  • Bruno Martino
  • Antonella Russo Rossi
  • Massimiliano Bonifacio
  • Claudio Fozza
  • Malgorzata Monika Trawinska
  • Daniele Cattaneo
  • Chiara Elena
  • Claudia Baratè
  • Fiorenza De Gregorio
  • Matteo Molica
  • Giorgio La Nasa
  • Robin Foà
  • Massimo Breccia
Original Article
  • 156 Downloads

Abstract

There is little information about cardiovascular adverse event (CV-AE) incidence in chronic myeloid leukemia (CML) patients treated with bosutinib in the real-life practice. We identified 54 consecutive CML patients treated with bosutinib, stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 40-month cumulative incidence of CV-AEs was 25.2 ± 8.1%. Patients with the SCORE of high–very high showed a significantly higher incidence of CV-AEs (55 ± 12.9% vs 9 ± 9.5%; p = 0.002). Overall, 9 CV-AEs were reported, with 2 deaths attributed to CV-AE. In conclusion, the SCORE assessment before starting treatment is helpful in identifying CV-AE high-risk patients during bosutinib treatment.

Keywords

Chronic myeloid leukemia Bosutinib Cardiovascular risk Acetylsalicylic acid 

Notes

Acknowledgments

We are deeply grateful to the patients who participated in this study.

Authors’ contributions

Conception and design: GC and MB

Collection and assembly of data: GC, OM, EA, AI, MA, EO, SG, GB, NS, LL, BM, ARR, MB, CF, MMT, DC, CE, CB, FDG, MM, GLN, RF, and MB

Statistical analysis: GC, OM, and FE

Manuscript writing: GC and MB

Final approval of the manuscript: GC, OM, EA, AI, MA, EO, SG, GB, NS, LL, BM, ARR, MB, CF, MMT, DC, CE, CB, FDG, MM, GLN, RF, and MB

Compliance with ethical standards

Competing interests

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

Data on patients were retrospectively collected in accordance with the 1975 guidelines of the Declaration of Helsinki.

References

  1. 1.
    Puttini M, Coluccia AML, Boschelli F, Cleris L, Marchesi E, Donella-Deana A, Ahmed S, Redaelli S, Piazza R, Magistroni V, Andreoni F, Scapozza L, Formelli F, Gambacorti-Passerini C (2006) In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res 66(23):11314–11322CrossRefPubMedGoogle Scholar
  2. 2.
    Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim D-W, Dyagil I, Glushko N, Milojkovic D, le Coutre P, Garcia-Gutierrez V, Reilly L, Jeynes-Ellis A, Leip E, Bardy-Bouxin N, Hochhaus A, Brümmendorf TH (2018) Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol Off J Am Soc Clin Oncol 36(3):231–237CrossRefGoogle Scholar
  3. 3.
    Brümmendorf TH, Cortes JE, de Souza CA, Guilhot F, Duvillié L, Pavlov D, Gogat K, Countouriotis AM, Gambacorti-Passerini C (2015) Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br J Haematol 168(1):69–81CrossRefPubMedGoogle Scholar
  4. 4.
    Kantarjian HM, Cortes JE, Kim D-W, Khoury HJ, Brümmendorf TH, Porkka K et al (2014) Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood. 123(9):1309–1318CrossRefPubMedGoogle Scholar
  5. 5.
    García-Gutiérrez V, Milojkovic D, Hernandez-Boluda JC, Claudiani S, Martin Mateos ML, Casado-Montero LF et al (2018) Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients. Ann Hematol 98(2):321-330CrossRefPubMedGoogle Scholar
  6. 6.
    Aghel N, Delgado DH, Lipton JH (2017) Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: preventive strategies and cardiovascular surveillance. Vasc Health Risk Manag 13:293–303CrossRefPubMedGoogle Scholar
  7. 7.
    Khoury HJ, Gambacorti-Passerini C, Brümmendorf TH (2018) Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia. Ann Oncol 29(3):578–587CrossRefPubMedGoogle Scholar
  8. 8.
    Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren WMM et al (2012) 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 (constituted by representatives of nine societies and by invited experts). Int J Behav Med 19(4):403–488CrossRefPubMedGoogle Scholar
  9. 9.
    Caocci G, Mulas O, Annunziata M, Luciano L, Bonifacio M, Orlandi EM, Pregno P, Galimberti S, Russo Rossi A, Abruzzese E, Iurlo A, Martino B, Sgherza N, Binotto G, Castagnetti F, Gozzini A, Fozza C, Bocchia M, Sicuranza A, Stagno F, Efficace F, Usala E, de Gregorio F, Scaffidi L, Elena C, Pirillo F, Baratè C, Trawinska MM, Cattaneo D, Labate C, Gugliotta G, Molica M, Specchia G, la Nasa G, Foà R, Breccia M (2018) Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice: identification of risk factors and the role of prophylaxis. Am J Hematol 93(7):E159–E161CrossRefPubMedGoogle Scholar
  10. 10.
    Breccia M, Molica M, Zacheo I, Serrao A, Alimena G (2015) Application of systematic coronary risk evaluation chart to identify chronic myeloid leukemia patients at risk of cardiovascular diseases during nilotinib treatment. Ann Hematol 94(3):393–397CrossRefPubMedGoogle Scholar
  11. 11.
    Rea D, Mirault T, Raffoux E, Boissel N, Andreoli AL, Rousselot P, Dombret H, Messas E (2015) Usefulness of the 2012 European CVD risk assessment model to identify patients at high risk of cardiovascular events during nilotinib therapy in chronic myeloid leukemia. Leukemia. 29(5):1206–1209CrossRefPubMedGoogle Scholar
  12. 12.
    Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Muller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saussele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 122(6):872–884CrossRefPubMedGoogle Scholar
  13. 13.
    Cross NCP, White HE, Müller MC, Saglio G, Hochhaus A (2012) Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 26(10):2172–2175CrossRefPubMedGoogle Scholar
  14. 14.
    Douxfils J, Haguet H, Mullier F, Chatelain C, Graux C, Dogné J-M (2016) Association between BCR-ABL tyrosine kinase inhibitors for chronic myeloid leukemia and cardiovascular events, major molecular response, and overall survival: a systematic review and meta-analysis. JAMA Oncol 2:625–632CrossRefPubMedGoogle Scholar
  15. 15.
    Cortes JE, Jean Khoury H, Kantarjian H, Brümmendorf TH, Mauro MJ, Matczak E, Pavlov D, Aguiar JM, Fly KD, Dimitrov S, Leip E, Shapiro M, Lipton JH, Durand JB, Gambacorti-Passerini C (2016) Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib. Am J Hematol 91(6):606–616CrossRefPubMedGoogle Scholar
  16. 16.
    Caocci G, Mulas O, Abruzzese E, Luciano L, Iurlo A, Attolico I et al (2019) Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart. Hematol Oncol Mar 20.  https://doi.org/10.1002/hon.2606. [Epub ahead of print]

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Giovanni Caocci
    • 1
    • 2
    Email author
  • Olga Mulas
    • 1
  • Elisabetta Abruzzese
    • 3
  • Alessandra Iurlo
    • 4
  • Mario Annunziata
    • 5
  • Ester Maria Orlandi
    • 6
  • Sara Galimberti
    • 7
  • Gianni Binotto
    • 8
  • Nicola Sgherza
    • 9
  • Luigia Luciano
    • 10
  • Bruno Martino
    • 11
  • Antonella Russo Rossi
    • 12
  • Massimiliano Bonifacio
    • 13
  • Claudio Fozza
    • 14
  • Malgorzata Monika Trawinska
    • 3
  • Daniele Cattaneo
    • 4
  • Chiara Elena
    • 6
  • Claudia Baratè
    • 7
  • Fiorenza De Gregorio
    • 10
  • Matteo Molica
    • 15
  • Giorgio La Nasa
    • 1
    • 2
  • Robin Foà
    • 15
  • Massimo Breccia
    • 15
  1. 1.Department of Medical Sciences and Public Health, Hematology and Transplant Center, Businco HospitalUniversity of CagliariCagliariItaly
  2. 2.SC Ematologia e CTMO, Ospedale Businco, Dipartimento di Scienze Mediche e Sanità PubblicaUniversità di CagliariCagliariItaly
  3. 3.Hematology UnitSant’Eugenio Hospital Tor Vergata UniversityRomeItaly
  4. 4.Hematology UnitFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  5. 5.Hematology UnitCardarelli HospitalNaplesItaly
  6. 6.Hematology Unit“Fondazione IRCCS Policlinico S. Matteo” University HospitalPaviaItaly
  7. 7.Department of Clinical and Experimental Medicine, Section of HematologyUniversity of PisaPisaItaly
  8. 8.Hematology UnitUniversity of PadovaPaduaItaly
  9. 9.Hematology and Transplant CenterCasa Sollievo della Sofferenza HospitalSan Giovanni RotondoItaly
  10. 10.Hematology Unit “Federico II” University of NaplesNaplesItaly
  11. 11.Hematology UnitAzienda Ospedaliera “Bianchi-Melacrino-Morelli”Reggio CalabriaItaly
  12. 12.Hematology and Transplants UnitUniversity of BariBariItaly
  13. 13.Department of Medicine, Section of HematologyUniversity of VeronaVeronaItaly
  14. 14.Department of Clinical and Experimental MedicineUniversity of SassariSassariItaly
  15. 15.Division of Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto ISapienza UniversityRomeItaly

Personalised recommendations