Skip to main content

Advertisement

SpringerLink
Log in

Use patterns of first-line inhibitors of tyrosine kinase and time to change to second-line therapy in chronic myeloid leukemia

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Chronic myeloid leukemia (CML) has a low incidence but a high burden of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI). Objective To determine the time from the start of a first-line TKI until it passes to second-line, and to establish the reasons for the change of therapy time. Setting Patients with Philadelphia-positive CML treated with some TKI. Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with information obtained from medical records, the time to change initial drugs to secondline therapy, and the reasons for change, were identified. Kaplan–Meier survival analysis was carried out. Main outcome measure A change in therapy to the secondline TKI and the final reason for the change of therapy. Results A total of 247 patients treated were found in 22 cities in Colombia with a mean age of 53.2 ± 15.2 years. The drug most used as initial therapy was imatinib; 53.8% of cases had to change to another TKI. 50% of patients changed therapy in 42 months, men in 24 and women in 67 months (95% CI 14.314–33.686; p = 0.001). Being male (OR 2.23; 95% CI 1.291–3.854; p = 0.004) and receiving hydroxyurea (OR 3.65; 95% CI 1.601–8.326; p = 0.002) were associated with a higher probability of switching to nilotinib or dasatinib, while receiving a new-generation TKI (OR 0.15; 95% CI 0.071–0.341; p < 0.001) reduced this risk. Conclusions A high proportion of patients needed to change to a second line with nilotinib and dasatinib management. It is necessary to obtain more real world evidence, to improve the effectiveness, adherence and safety of the treatment.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Instituto Nacional de Cancerología - ESE. INC. Colombia. Cáncer en cifras, Incidencias por tipo de cáncer 2002–2006 (internet). http://www.cancer.gov.co/cancer_en_cifras. Cited 21 Feb 2017.

  2. Hehlmann R, Hochhaus A, Baccarani M. European Leukemia Net: chronic myeloid leukaemia. Lancet. 2007;370(9584):342–50.

    Article  CAS  PubMed  Google Scholar 

  3. Wetzler M, Marcucci G, Bloomfield CD. Acute and Chronic Myeloid Leukemia. Chapter 109. In: Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J, editors. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill, Medical Pub. Division; 2011. p. 905–18.

    Google Scholar 

  4. Apperley JF. Chronic myeloid leukaemia. Lancet. 2015;385(9976):1447–59.

    Article  PubMed  Google Scholar 

  5. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–7.

    Article  CAS  PubMed  Google Scholar 

  6. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–17.

    Article  CAS  PubMed  Google Scholar 

  7. Schiffer CA. BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med. 2007;357(3):258–65.

    Article  CAS  PubMed  Google Scholar 

  8. Balabanov S, Braig M, Brümmendorf TH. Current aspects in resistance against tyrosine kinase inhibitors in chronic myelogenous leukemia. Drug Discov Today Technol. 2014;11:89–99.

    Article  PubMed  Google Scholar 

  9. Stenehjem DD, Albright F, Kuo KL, Raimundo K, Bauer H, Shami PJ, et al. Response monitoring, tolerability, and effectiveness of imatinib treatment for chronic myeloid leukemia in a retrospective research database. J Natl Compr Cancer Netw. 2014;12(8):1113–21.

    Article  CAS  Google Scholar 

  10. Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer. 2007;7(5):345–56.

    Article  CAS  PubMed  Google Scholar 

  11. Goulden S, Sutcliffe F, Stevens A. NICE guidance on dasatinib, high-dose imatinib, and nilotinib for patients with CML who are resistant or intolerant to imatinib. Lancet Oncol. 2012;13(2):127–8.

    Article  PubMed  Google Scholar 

  12. Romero M, Chávez D, De Los Ríos M, Alvis-Guzmán N. Cost-effectiveness of nilotinib, dasatinib and imatinib as first-line treatment for chronic myeloid leukemia in Colombia, 2012. Biomedica. 2014;34(1):48–59.

    Article  PubMed  Google Scholar 

  13. Guevara G, González JA, Lopera DE, González M, Saavedra JD, Lobaton JF, et al. Follow-up of the tumor load in patients with de novo chronic myeloid leukemia and in complete cytogenetic remission treated with imatinib in Colombia. Colomb Med (Cali). 2012;43(4):267–72.

    Google Scholar 

  14. Jabbour EJ, Cortes JE, Kantarjian HM. Resistance to tyrosine kinase inhibition therapy for chronic myelogenous leukemia: a clinical perspective and emerging treatment options. Clin Lymphoma Myeloma Leuk. 2013;13(5):515–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jabbour E, Kantarjian HM, Jones D, Shan J, O’Brien S, Reddy N, et al. Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy. Blood. 2009;113:2154–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Henk HJ, Woloj M, Shapiro M, Whiteley J. Real-world analysis of tyrosine kinase inhibitor treatment patterns among patients with chronic myeloid leukemia in the United States. Clin Ther. 2015;37(1):124–33.

    Article  PubMed  Google Scholar 

  17. Mitra D, Trask PC, Iyer S, Candrilli SD, Kaye JA. Patient characteristics and treatment patterns in chronic myeloid leukemia: evidence from a multi-country retrospective medical record chart review study. Int J Hematol. 2012;95(3):263–73.

    Article  CAS  PubMed  Google Scholar 

  18. Whiteley J, Iyer S, Candrilli SD, Kaye JA. Treatment patterns and prognostic indicators of response to therapy among patients with chronic myeloid leukemia in Australia, Canada, and South Korea. Curr Med Res Opin. 2015;31(2):299–314.

    Article  CAS  PubMed  Google Scholar 

  19. Chen L, Guérin A, Xie J, Wu EQ, Yu AP, Ericson SG, et al. Monitoring and switching patterns of patients with chronic myeloid leukemia treated with imatinib in community settings: a chart review analysis. Curr Med Res Opin. 2012;28(11):1831–9.

    Article  CAS  PubMed  Google Scholar 

  20. Saleh MN, Haislip S, Sharpe J, Hess T, Gilmore J, Jackson J, et al. Assessment of treatment and monitoring patterns and subsequent outcomes among patients with chronic myeloid leukemia treated with imatinib in a community setting. Curr Med Res Opin. 2014;30(4):529–36.

    Article  CAS  PubMed  Google Scholar 

  21. Kim TD, Schwarz M, Nogai H, Grille P, Westermann J, Plöckinger U. Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia. Thyroid. 2010;20(11):1209–14.

    Article  CAS  PubMed  Google Scholar 

  22. Yoshizato T, Nannya Y, Yoshiki Y, Nakamura F, Imai Y, Ichikawa M, et al. Nilotinib-induced hypothyroidism in a patient with chronic myeloid leukemia. Int J Hematol. 2011;93(3):400–2.

    Article  PubMed  Google Scholar 

  23. Edesa WA, Abdel-malek RR. Impact of imatinib interruption and duration of prior hydroxyurea on the treatment outcome in patients with chronic myeloid leukemia: single institution experience. J Egypt Natl Canc Inst. 2015;27(2):69–75.

    Article  PubMed  Google Scholar 

  24. Payandeh M, Sadeghi M, Sadeghi E. Treatment and survival in patients with chronic myeloid leukemia in a chronic phase in West Iran. Asian Pac J Cancer Prev. 2015;16(17):7555–9.

    Article  PubMed  Google Scholar 

  25. Pulte D, Barnes B, Jansen L, Eisemann N, Emrich K, Gondos A, GEKID Cancer Survival Working Group, et al. Population level survival of patients with chronic myelocytic leukemia in Germany compared to the US in the early 21st century. J Hematol Oncol. 2013;6(1):70.

    Article  PubMed  PubMed Central  Google Scholar 

  26. de Almeida MH, Fogliatto L, Couto D. Importance of adherence to BCR-ABL tyrosine-kinase inhibitors in the treatment of chronic myeloid leukemia. Rev Bras Hematol Hemoter. 2014;36(1):54–9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Efficace F, Baccarani M, Rosti G, Cottone F, Castagnetti F, Breccia M, et al. Investigating factors associated with adherence behaviour in patients with chronic myeloid leukemia: an observational patient-centered outcome study. Br J Cancer. 2012;107(6):904–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Noens L, van Lierde MA, De Bock R, Verhoef G, Zachée P, Berneman Z, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113(22):5401–11.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The authors want to thank the Universidad Tecnológica de Pereira, Audifarma S.A. and Novartis Colombia for their support.

Funding

This study received funding from the Universidad Tecnológica de Pereira, Audifarma S.A. and Novartis of Colombia.

Conflicts of interest

The authors declare that Novartis of Colombia financed the data collection process. There was no intervention in the stages of processing, analysis or publication of that data. No non-financial conflicts of interest exist for any of the authors.

Author information

Authors and Affiliations

  1. Grupo de Investigación en Farmacoepidemiología y Farmacovigilancia, Facultad Ciencias de la Salud-Programa de Medicina, Universidad Tecnológica de Pereira- Audifarma S.A., Paraje la Julita, AA: 97, Pereira, Risaralda, 660003, Colombia

    Jorge Enrique Machado-Alba & Manuel Enrique Machado-Duque

Authors
  1. Jorge Enrique Machado-Alba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuel Enrique Machado-Duque
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jorge Enrique Machado-Alba.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Machado-Alba, J.E., Machado-Duque, M.E. 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 39, 851–859 (2017). https://doi.org/10.1007/s11096-017-0484-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-017-0484-9

Keywords

Search

Navigation