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Vol. 130, No. 1, 2013
Issue release date: June 2013
Acta Haematol 2013;130:16–22

Adherence to Tyrosine Kinase Inhibitor Therapy for Chronic Myeloid Leukemia: A Brazilian Single-Center Cohort

de Almeida M.H. · Pagnano K.B.B. · Vigorito A.C. · Lorand-Metze I. · de Souza C.A.
Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil

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The introduction of oral tyrosine kinase inhibitors (TKIs) has dramatically improved outcomes in chronic myeloid leukemia (CML) patients. However, treatment success is directly related to good long-term adherence. Adherence to TKI therapy was evaluated in 137 CML patients over a period of 1 year. Three different methods were used to evaluate adherence: the Morisky questionnaire, a medication diary and the medication possession ratio (MPR). MPR was the most effective method of assessing adherence (median adherence 96.5%; p = 0.0001), duration of TKI treatment was the variable that most impacted adherence (p = 0.03), and the MPR was inversely correlated to the duration of therapy. Additionally, participation in clinical trials, better quality of life as reported by patients and higher socioeconomic status were all related to better compliance (p = 0.02, 0.007 and 0.01, respectively). For patients treated with imatinib for 24–48 months (n = 22), individuals with major molecular response (MMR) had a significantly better MPR than those who failed to achieve MMR (p = 0.04). In this group, the mean MPR was 87% for the population without apparent molecular response and 96% for those achieving MMR; however, only 24% of the patients were completely adherent to TKI treatment.

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  1. Darkow T, Henk HJ, Thomas SK, Feng W, Baladi JF, Goldberg GA, Cortes J: Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 2007;25:481–496.
  2. Kripalani S, Yao X, Haynes RB: Interventions to enhance medication adherence in chronic medical conditions: a systematic review. Arch Intern Med 2007;167:540–550.
  3. Martin LR, Williams SL, Haskard KB, Dimatteo MR: The challenge of patient adherence. Ther Clin Risk Manag 2005;1:189–199.

    External Resources

  4. Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS: Impact of medication adherence on hospitalization risk and healthcare cost. Med Care 2005;43:521–530.
  5. Sabate E: Adherence to long-term therapies: evidence for action. Geneva, World Health Organization, 2003.
  6. Osterberg L, Blaschke T: Adherence to medication. N Engl J Med 2005;353:487–497.
  7. Waterhouse DM, Calzone KA, Mele C, Brenner DE: Adherence to oral tamoxifen: a comparison of patient self-report, pill counts, and microelectronic monitoring. J Clin Oncol 1993;11:1189–1197.
  8. Jonsson S, Olsson B, Soderberg J, Wadenvik H: Good adherence to imatinib therapy among patients with chronic myeloid leukemia – a single-center observational study. Ann Hematol 2012;91:679–685.
  9. Ibrahim AR, Eliasson L, Apperley JF, Milojkovic D, Bua M, Szydlo R, Mahon FX, Kozlowsk K, Paliompeis C, Foroni L, Khorashad JS, Bazeos A, Molimard M, Rezvani K, Gerrad G, Goldman J, Marin D: Poor adherence is the main reason for loss of CCyR and imatinib failure for CML patients on long-term therapy. Blood 2011;117:3733–3736.
  10. Yoshida C, Komeno T, Hori M, Kimura T, Fujii M, Okoshi Y, Chiba S, Hasegawa Y, Mukai HY, Ito T, Shimizu S, Kamoshita M, Kudo D, Shinagawa A, Chikatsu N, Monma Y, Watanabe N, Kojima H: Adherence to the standard dose of imatinib, rather than dose adjustment based on its plasma concentration, is critical to achieve a deep molecular response in patients with chronic myeloid leukemia. Int J Hematol 2011;93:618–623.
  11. Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, Bua M, Apperley JF, Szydlo R, Desai R, Kozlowski K, Paliompeis C, Latham V, Foroni L, Molimard M, Reid A, Rezvani K, de Lavallade H, Guallar C, Goldman J, Krorashad JS: Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol 2010;28:2381–2388.
  12. Noens L, van Lierde MA, De Bock R, Verhoef G, Zachee P, Berneman Z, Martiat P, Mineur P, Van Eygen K, MacDonald K, De Geest S, Albrecht T, Abraham I: Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood 2009;113:5401–5411.
  13. Baeninger R, de Martino Jannuzzi P: Qualificação socioeconômica e demográfica das classes da escala abipeme. Revista Administração 1996;31:82–90.
  14. EuroQol – a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy 1990;16:199–208.
  15. Morisky DE, Green LW, Levine DM: Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 1986;24:67–74.
  16. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, Apperley, J, Cervantes F, Cortes J, Deininger M, Gratwohl, A, Guilhot F, Horowitz M, Hughes T, Kantarjian H, Larson R, Niederwieser D, Silver R, Hehlmann R: Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809–1820.
  17. Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG: Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006;354:2542–2551.
  18. O’Brien SG, Deininger MW: Imatinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia. Semin Hematol 2003;40:26–30.
  19. Mauro MJ, O’Dwyer M, Heinrich MC, Druker BJ: STI571: a paradigm of new agents for cancer therapeutics. J Clin Oncol 2002;20:325–334.
  20. Blaschke TF, Osterberg L, Vrijens B, Urquhart J: Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Ann Rev Pharmacol Toxicol 2012;52:275–301.
  21. Partridge AH, Avorn J, Wang PS, Winer EP: Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst 2002;94:652–661.
  22. Eliasson L, Clifford S, Barber N, Marin D: Exploring chronic myeloid leukemia patients’ reasons for not adhering to the oral anticancer drug imatinib as prescribed. Leuk Res 2011;35:626–630.
  23. Ganesan P, Sagar TG, Dubashi B, Rahendranath R, Kannan K, Cyriac S, Nandennavar M: Nonadherence to imatinib adversely affects event free survival in chronic phase chronic myeloid leukemia. Am J Hematol 2011;86:471–474.
  24. Jabbour E, Saglio G, Radich J, Kantarjian H: Adherence to BCR-ABL inhibitors: issues for CML therapy. Clin Lymphoma Myeloma Leuk 2012;23:1–7.
  25. Breccia M, Efficace F, Alimena G: Adherence to treatment is a complex and multifaceted issue that can substantially alter the outcome of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Leuk Res 2012;36:804–805.
  26. Gater A, Heron L, Abetz-Webb L, Coobs J, Simmons J, Guilhot F, Rea D: Adherence to oral tyrosine kinase inhibitor therapies in chronic myeloid leukemia. Leuk Res 2012;36:817–825.
  27. DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW: Patient adherence and medical treatment outcomes: a meta-analysis. Med Care 2002;40:794–811.
  28. Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioff A, Emile JF, Chabaud S, Perol D, Blay JY: Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol 2010;11:942–949.

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