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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Data and medical charts are available at the Italian institutions involved in the study.
References
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):11314–11322
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):231–237
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):69–81
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):1309–1318
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):321-330
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 13:293–303
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):578–587
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):403–488
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–E161
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):393–397
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):1206–1209
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):872–884
Cross NCP, White HE, Müller MC, Saglio G, Hochhaus A (2012) Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 26(10):2172–2175
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 2:625–632
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):606–616
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]
Acknowledgments
We are deeply grateful to the patients who participated in this study.
Author information
Authors and Affiliations
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
Corresponding author
Ethics declarations
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.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Caocci, G., Mulas, O., Abruzzese, E. et al. Incidence and evaluation of predisposition to cardiovascular toxicity in chronic myeloid leukemia patients treated with bosutinib in the real-life practice. Ann Hematol 98, 1885–1890 (2019). https://doi.org/10.1007/s00277-019-03705-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-019-03705-y