Skip to main content

Advertisement

Log in

Pattern of Use and Long-Term Safety of Tyrosine Kinase Inhibitors: A Decade of Real-World Management of Chronic Myeloid Leukemia

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and Objectives

First-line treatment of chronic phase (CP) chronic myeloid leukemia (CML) is based on the first-generation tyrosine kinase inhibitor (TKI) imatinib or the second-generation TKIs dasatinib or nilotinib. Thanks to the efficacy of TKIs, CML has switched from a fatal to a ‘chronic’ pathology, and data from clinical trials have become insufficient to drive physicians’ prescription choices and address long-term treatment outcomes. On the brink of commercialization of generic imatinib, this study aims to evaluate the therapeutic pattern of CP-CML and the occurrence of adverse events (AEs) over a decade of local real clinical practice.

Methods

A retrospective cohort study was performed on CP-CML patients followed up in the Local Health Unit of Treviso (Veneto Region, Italy) during the period 2005–2015. Data were captured from both administrative databases and physicians’ patient diaries.

Results

Of 81 CP-CML patients, 73 were treated with first-line imatinib; among the second-generation TKIs, only nilotinib was used (n = 8). Overall, 38% of imatinib-treated subjects needed to switch, mainly due to intolerance, whereas no switches occurred in the nilotinib cohort. Osteoarticular pain was the most common AE and was significantly more frequent in the imatinib cohort (68.49 vs. 25.00%, p = 0.022). Other common AEs were dermatologic manifestations, asthenia, and diarrhea.

Conclusion

Although based on a small population, this study represents an unbiased reference on the long-term management of CML in an Italian clinical setting. Our results indicate a better profile of first-line nilotinib, both in terms of persistency and tolerability. AEs remain a major concern, highlighting the importance of close monitoring.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Faderl S, Kantarjian HM, Talpaz M. Chronic myelogenous leukemia: update on biology and treatment. Oncology. 1999;13(2):169–80.

    PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  Google Scholar 

  3. Nowell PCHD. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1497.

    Google Scholar 

  4. Rowley JD. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243(5405):290–3.

    Article  CAS  Google Scholar 

  5. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247(4944):824–30.

    Article  CAS  Google Scholar 

  6. Quintas-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc. 2006;81(7):973–88.

    Article  CAS  Google Scholar 

  7. Chereda B, Melo JV. Natural course and biology of CML. Ann Hematol. 2015;94(Suppl 2):S107–21.

    Article  Google Scholar 

  8. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84.

    Article  CAS  Google Scholar 

  9. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63(4):789–99.

    CAS  PubMed  Google Scholar 

  10. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90(11):850–8.

    Article  CAS  Google Scholar 

  11. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118(3):686–92.

    Article  CAS  Google Scholar 

  12. Kantarjian H, O’Brien S, Jabbour E, Garcia-Manero G, Quintas-Cardama A, Shan J, et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood. 2012;119(9):1981–7.

    Article  CAS  Google Scholar 

  13. Mauro MJ, Davis C, Zyczynski T, Khoury HJ. The role of observational studies in optimizing the clinical management of chronic myeloid leukemia. Ther Adv Hematol. 2015;6(1):3–14.

    Article  Google Scholar 

  14. Rohrbacher M, Berger U, Hochhaus A, Metzgeroth G, Adam K, Lahaye T, et al. Clinical trials underestimate the age of chronic myeloid leukemia (CML) patients. Incidence and median age of Ph/BCR-ABL-positive CML and other chronic myeloproliferative disorders in a representative area in Germany. Leukemia. 2009;23(3):602–4.

    Article  CAS  Google Scholar 

  15. Latagliata R, Breccia M, Carmosino I, Cannella L, De Cuia R, Diverio D, et al. “Real-life” results of front-line treatment with Imatinib in older patients (≥ 65 years) with newly diagnosed chronic myelogenous leukemia. Leuk Res. 2010;34(11):1472–5.

    Article  CAS  Google Scholar 

  16. Berger U, Maywald O, Pfirrmann M, Lahaye T, Hochhaus A, Reiter A, et al. Gender aspects in chronic myeloid leukemia: long-term results from randomized studies. Leukemia. 2005;19(6):984–9.

    Article  CAS  Google Scholar 

  17. Hoglund M, Sandin F, Simonsson B. Epidemiology of chronic myeloid leukaemia: an update. Ann Hematol. 2015;94(Suppl 2):S241–7.

    Article  Google Scholar 

  18. Saglio G, Hochhaus A, Goh YT, Masszi T, Pasquini R, Maloisel F, et al. Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily. Cancer. 2010;116(16):3852–61.

    Article  CAS  Google Scholar 

  19. Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011;12(9):841–51.

    Article  CAS  Google Scholar 

  20. Michallet M, Tulliez M, Corm S, Gardembas M, Huguet F, Oukessou A, et al. Management of chronic myeloid leukaemia in clinical practice in France: results of the French subset of patients from the UNIC study. Curr Med Res Opin. 2010;26(2):307–17.

    Article  CAS  Google Scholar 

  21. Cortes J, Kantarjian H. How I treat newly diagnosed chronic phase CML. Blood. 2012;120(7):1390–7.

    Article  CAS  Google Scholar 

  22. Novartis pharmaceuticals. A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph +) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) (ENESTnd). Available at: https://clinicaltrials.gov/ct2/show/NCT00471497. Accessed 15 March 2017.

  23. Saussele S, Richter J, Hochhaus A, Mahon FX. The concept of treatment-free remission in chronic myeloid leukemia. Leukemia. 2016;30(8):1638–47.

    Article  CAS  Google Scholar 

  24. Castagnetti F, Di Raimondo F, De Vivo A, Spitaleri A, Gugliotta G, Fabbiano F, et al. A population-based study of chronic myeloid leukemia patients treated with imatinib in first line. Am J Hematol. 2017;92(1):82–7.

    Article  CAS  Google Scholar 

  25. Machado-Alba JE, Machado-Duque ME. Use patterns of first-line inhibitors of tyrosine kinase and time to change to second-line therapy in chronic myeloid leukemia. Int J Clin Pharm. 2017;39(4):851–9.

    Article  CAS  Google Scholar 

  26. Mughal TI, Radich JP, Deininger MW, Apperley JF, Hughes TP, Harrison CJ, et al. Chronic myeloid leukemia: reminiscences and dreams. Haematologica. 2016;101(5):541–58.

    Article  CAS  Google Scholar 

  27. Steegmann JL, Baccarani M, Breccia M, Casado LF, Garcia-Gutierrez V, Hochhaus A, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30(8):1648–71.

    Article  CAS  Google Scholar 

  28. Baccarani M, Castagnetti F, Gugliotta G, Rosti G. A review of the European LeukemiaNet recommendations for the management of CML. Ann Hematol. 2015;94(Suppl 2):S141–7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alessandra Bettiol.

Ethics declarations

Funding

No funding was received for this study.

Conflicts of Interest

Alessandra Bettiol, Ettore Marconi, Niccolò Lombardi, Giada Crescioli, Filippo Gherlinzoni, Thomas Walley, Alfredo Vannacci, Alessandro Chinellato and Pietro Giusti declare that they have no conflicts of interest.

Ethical Approval

The Ethics Committee of the Local Health Unit n.2 of Treviso (Regione Veneto, Comitato Etico per la Sperimentazione Clinica delle Province di Belluno e Treviso) notified the present study on 15 December 2016 (Studio n. XLV/RPA—AULSS 9—Studio Osservazionale—No Profit).

Informed Consent

Formal consent is not required for this type of study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bettiol, A., Marconi, E., Lombardi, N. et al. Pattern of Use and Long-Term Safety of Tyrosine Kinase Inhibitors: A Decade of Real-World Management of Chronic Myeloid Leukemia. Clin Drug Investig 38, 837–844 (2018). https://doi.org/10.1007/s40261-018-0676-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-018-0676-7

Navigation