Advertisement

Current Hematologic Malignancy Reports

, Volume 11, Issue 2, pp 80–85 | Cite as

Quality of Life and Long-Term Therapy in Patients with Chronic Myeloid Leukemia

  • Kathryn E. Flynn
  • Ehab Atallah
Chronic Myeloid Leukemias (J Pinilla-Ibarz, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Chronic Myeloid Leukemias

Abstract

Since the development of imatinib and other tyrosine kinase inhibitors (TKIs), the prognosis for patients with chronic myeloid leukemia (CML) has markedly improved, such that most patients diagnosed with CML can now expect to live with their disease rather than die from it. However, most patients will require long-term treatment, which has deleterious effects on health-related quality of life. We review recent literature on drug-related adverse effects, long-term medication adherence, limitations to fertility and pregnancy, effects on cognitive function, ability to work, financial toxicity, pediatric populations, and treatment discontinuation. While patients with CML are fortunate to have excellent therapies available to control their disease, many are unable to lead normal lives, which challenges the notion that research is no longer needed in CML. Curing CML, i.e., no detectable disease and no need for daily medications, should remain the ultimate goal.

Keywords

Chronic myeloid leukemias Tyrosine kinase inhibitors Therapy Quality of life 

Notes

Acknowledgments

Drs Flynn and Atallah were supported by grant R01 CA184798 from the National Cancer Institute. Dr Flynn was supported in part by the Research and Education Program Fund, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin.

Compliance with Ethical Standards

Conflict of Interest

Kathryn E. Flynn declares no potential conflicts of interest.

Ehab Atallah reports personal fees from BMS and Pfizer.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Saussele S, Stein M, Gil A, Kossak-Roth U, Lauseker M, Proetel U, et al. Health-related quality of life impairment in patients with chronic myeloid leukemia: results of a German cross-sectional study of patients registered in prospective. Control Clin Trials Blood. 2015;126:2773.Google Scholar
  2. 2.
    Efficace F, Baccarani M, Breccia M, Cottone F, Alimena G, Deliliers GL, et al. Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib. Leukemia. 2013;27:1511–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Efficace F, Cardoni A, Cottone F, Vignetti M, Mandelli F. Tyrosine-kinase inhibitors and patient-reported outcomes in chronic myeloid leukemia: a systematic review. Leuk Res. 2013;37:206–13.CrossRefPubMedGoogle Scholar
  4. 4.
    Guerin A, Chen L, Ionescu-Ittu R, Marynchenko M, Nitulescu R, Hiscock R, et al. Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase. Curr Med Res Opin. 2014;30:2317–28.CrossRefPubMedGoogle Scholar
  5. 5.••
    Kalmanti L, Saussele S, Lauseker M, Muller MC, Dietz CT, Heinrich L, et al. Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV. Leukemia. 2015;29:1123–32. 10-year follow-up of imatinib therapy. A comprehensive analysis of imatinib therapy in CML.CrossRefPubMedGoogle Scholar
  6. 6.
    Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boqué C, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Cortes JE, Saglio G, Baccarani M, Kantarjian HM, Mayer J, Boqué C, et al. Final study results of the phase 3 dasatinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) trial (DASISION, CA180-056). Blood. 2014;124:152.Google Scholar
  8. 8.••
    Shah NP, Guilhot F, Cortes JE, Schiffer CA, le Coutre P, Brümmendorf TH, et al. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood. 2014;123:2317–24. Long term follow up of patients on dasatinib demonstrating no increase in rate of AEs with longer follow up.CrossRefPubMedGoogle Scholar
  9. 9.
    Brümmendorf TH, Cortes JE, de Souza CA, Guilhot F, Duvillié L, Pavlov D, et al. 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. 2015;168:69–81.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Saglio G, Kim D-W, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus Imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.CrossRefPubMedGoogle Scholar
  11. 11.
    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;12:841–51.CrossRefPubMedGoogle Scholar
  12. 12.
    Larson RA, Hochhaus A, Hughes TP, Clark RE, Etienne G, Kim DW, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia. 2012;26:2197–203.CrossRefPubMedGoogle Scholar
  13. 13.
    Saglio G, Hochhaus A, Hughes TP, Clark RE, Nakamae H, Kim D-W, et al. ENESTnd update: nilotinib (NIL) vs imatinib (IM) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and the impact of early molecular response (EMR) and Sokal risk at diagnosis on long-term outcomes. Blood. 2013;122:92.Google Scholar
  14. 14.••
    Mo XD, Jiang Q, Xu LP, Liu DH, Liu KY, Jiang B, et al. Health-related quality of life of patients with newly diagnosed chronic myeloid leukemia treated with allogeneic hematopoietic SCT versus imatinib. Bone Marrow Transplant. 2014;49:576–80. Unexpected results of similar QOL between patients on TKIs and those receiving HCT.CrossRefPubMedGoogle Scholar
  15. 15.
    Chen TC, Chen LC, Huang YB, Chang CS. Imatinib adherence associated clinical outcomes of chronic myeloid leukaemia treatment in Taiwan. Int J Clin Pharmacol. 2014;36:172–81.CrossRefGoogle Scholar
  16. 16.
    Noens L, van Lierde MA, De Bock R, Verhoef G, Zachee 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;113:5401–11.CrossRefPubMedGoogle Scholar
  17. 17.
    Anderson KR, Chambers CR, Lam N, Yau PS, Cusano F, Savoie ML, et al. Medication adherence among adults prescribed imatinib, dasatinib, or nilotinib for the treatment of chronic myeloid leukemia. J Oncol Pharm Pract. 2015;21:19–25.CrossRefPubMedGoogle Scholar
  18. 18.
    Breccia M, Efficace F, Sica S, Abruzzese E, Cedrone M, Turri D, et al. Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients. Leuk Res. 2015;39:1055–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Efficace F, Rosti G, Cottone F, Breccia M, Castagnetti F, Iurlo A, et al. Profiling chronic myeloid leukemia patients reporting intentional and unintentional non-adherence to lifelong therapy with tyrosine kinase inhibitors. Leuk Res. 2014;38:294–8.CrossRefPubMedGoogle Scholar
  20. 20.•
    Hirji I, Gupta S, Goren A, Chirovsky DR, Moadel AB, Olavarria E, et al. Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient’s perspective. Health Qual Life Outcomes. 2013;11:167. Important data correlating QOL with medication experience.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Höglund M, Sandin F, Hellström K, Björeman M, Björkholm M, Brune M, et al. Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry. Blood. 2013;122:1284–92.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Breccia M, Cannella L, Montefusco E, Frustaci A, Pacilli M, Alimena G. Male patients with chronic myeloid leukemia treated with imatinib involved in healthy pregnancies: report of five cases. Leuk Res. 2008;32:519–20.CrossRefPubMedGoogle Scholar
  23. 23.
    Ramasamy K, Hayden J, Lim Z, Mufti GJ, Ho AY. Successful pregnancies involving men with chronic myeloid leukaemia on imatinib therapy. Br J Haematol. 2007;137:374–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Ault P, Kantarjian H, O’Brien S, Faderl S, Beran M, Rios MB, et al. Pregnancy among patients with chronic myeloid leukemia treated with imatinib. J Clin Oncol. 2006;24:1204–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Pye SM, Cortes J, Ault P, Hatfield A, Kantarjian H, Pilot R, et al. The effects of imatinib on pregnancy outcome. Blood. 2008;111:5505–8.CrossRefPubMedGoogle Scholar
  26. 26.••
    Palani R, Milojkovic D, Apperley JF. Managing pregnancy in chronic myeloid leukaemia. Ann Hematol. 2015;94:167–76. Excellent review on pregnancy and outcome.CrossRefGoogle Scholar
  27. 27.
    Chang G, Meadows ME, Smallwood JA, Antin JH, Orav EJ. Cognitive and other predictors of change in quality of life one year after treatment for chronic myelogenous leukemia or myelodysplastic syndrome. J Neuropsychiatry Clin Neurosci. 2014;26:249–57.CrossRefPubMedGoogle Scholar
  28. 28.
    Hamerschlak N, de Souza C, Cornacchioni AL, Pasquini R, Tabak D, Spector N, et al. Quality of life of chronic myeloid leukemia patients in Brazil: ability to work as a key factor. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2014;22:2113–8.Google Scholar
  29. 29.
    McNulty J, Khera N. Financial hardship—an unwanted consequence of cancer treatment. Curr Hematol Malig Rep. 2015;10:205–12.CrossRefPubMedGoogle Scholar
  30. 30.
    Dusetzina SB, Winn AN, Abel GA, Huskamp HA, Keating NL. Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. J Clin Oncol. 2014;32:306–11.CrossRefPubMedGoogle Scholar
  31. 31.
    Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013;121:4439–42.CrossRefPubMedCentralGoogle Scholar
  32. 32.
    Millot F, Guilhot J, Baruchel A, Petit A, Leblanc T, Bertrand Y, et al. Growth deceleration in children treated with imatinib for chronic myeloid leukaemia. Eur J Cancer. 2014;50:3206–11.CrossRefPubMedGoogle Scholar
  33. 33.
    Shima H, Tokuyama M, Tanizawa A, Tono C, Hamamoto K, Muramatsu H, et al. Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia. J Pediatr. 2011;159:676–81.CrossRefPubMedGoogle Scholar
  34. 34.
    Narayanan KR, Bansal D, Walia R, Sachdeva N, Bhansali A, Varma N, et al. Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF-1 axis. Pediatr Blood Cancer. 2013;60:1148–53.CrossRefPubMedGoogle Scholar
  35. 35.
    Seshadri T, Seymour JF, McArthur GA. Oligospermia in a patient receiving imatinib therapy for the hypereosinophilic syndrome. N Engl J Med. 2004;351:2134–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Nurmio M, Toppari J, Zaman F, Andersson AM, Paranko J, Soder O, et al. Inhibition of tyrosine kinases PDGFR and C-Kit by imatinib mesylate interferes with postnatal testicular development in the rat. Int J Androl. 2007;30:366–76. discussion 376.CrossRefPubMedGoogle Scholar
  37. 37.
    Hijiya N, Schultz KR, Metzler M, Millot F, Suttorp M. Pediatric chronic myeloid leukemia is a unique disease that requires a different approach. Blood. 2016;127:392–9.CrossRefPubMedGoogle Scholar
  38. 38.••
    Mahon FX. Discontinuation of tyrosine kinase therapy in CML. Ann Hematol. 2015;94 Suppl 2:S187–93. Excellent review on the unique challenges in patients’ children and adolescents with CML.CrossRefPubMedGoogle Scholar
  39. 39.
    Richter J, Söderlund S, Lübking A, Dreimane A, Lotfi K, Markevärn B, et al. Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome? J Clin Oncol. 2014;32:2821–3.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Medicine, Center for Patient Care and Outcomes ResearchMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of MedicineMedical College of WisconsinMilwaukeeUSA

Personalised recommendations