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Treatment-Free Remission in CML: the US Perspective

  • Guru Subramanian Guru MurthyEmail author
  • Ehab Atallah
Chronic Myeloid Leukemias (M Mauro, Section Editor)
  • 75 Downloads
Part of the following topical collections:
  1. Topical Collection on Chronic Myeloid Leukemias

Abstract

Purpose of Review

Chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI) have near-normal life expectancy. However, lifelong TKI therapy is associated with reduced quality of life and significant economic burden. Currently, the management of CML is shifting from continuous TKI therapy towards the goal of TKI cessation which is discussed in this review.

Recent Findings

Several studies in the last decade have demonstrated the feasibility and safety of TKI discontinuation in selected patients with CML who achieve deep and sustained molecular response with TKI. This has moved prime-time into clinical practice although open questions remain in terms of understanding the disease biology that leads to successful TKI cessation in some patients while not in others.

Summary

Cessation of TKI for CML patients is a feasible approach. Ongoing research aims to find out optimal strategies to sustain ongoing treatment-free remission (TFR) and increase the number of patients who achieve TFR.

Keywords

Leukemia Myeloid Chronic Treatment Discontinuation 

Notes

Compliance with Ethical Standards

Conflict of Interest

Ehab Atallah reports personal fees from Novartis, BMS, and Pfizer, outside the submitted work. Guru Subramanian Guru Murthy declares no conflict of interest.

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.
    Sasaki K, Strom SS, O’Brien S, Jabbour E, Ravandi F, Konopleva M, et al. Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol. 2015;2(5):e186–93.  https://doi.org/10.1016/S2352-3026(15)00048-4.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Huang X, Cortes J, Kantarjian H. Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer. 2012;118(12):3123–7.  https://doi.org/10.1002/cncr.26679.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    •• NCCN Clinical practice guidelines in oncology. Chronic myeloid leukemia version 4.2018 - Jan 24, 2018. First practice guidelines in US for TKI cessation. Google Scholar
  4. 4.
    Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260–70.  https://doi.org/10.1056/NEJMoa1002315.CrossRefPubMedGoogle Scholar
  5. 5.
    Saglio G, Kim DW, 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(24):2251–9.  https://doi.org/10.1056/NEJMoa0912614.CrossRefPubMedGoogle Scholar
  6. 6.
    Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36(3):231–7.  https://doi.org/10.1200/JCO.2017.74.7162.CrossRefPubMedGoogle Scholar
  7. 7.
    Branford S, Seymour JF, Grigg A, Arthur C, Rudzki Z, Lynch K, et al. BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria. Clin Cancer Res. 2007;13(23):7080–5.  https://doi.org/10.1158/1078-0432.CCR-07-0844.CrossRefPubMedGoogle Scholar
  8. 8.
    Chomel JC, Bonnet ML, Sorel N, Bertrand A, Meunier MC, Fichelson S, et al. Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease. Blood. 2011;118:3657–60.  https://doi.org/10.1182/blood-2011-02-335497.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Goldberg S, Hamarman S. Patients with chronic myelogenous leukemia may not want to discontinue tyrosine kinase inhibitor therapy. Blood. 2015;126:1584 (abstract).Google Scholar
  10. 10.
    Flynn K, Schiffer C, Thompson J, Atallah E. Patient decision making about treatment discontinuation. Presented at ESH John Goldman Conference on CML, 2016 (abstract).Google Scholar
  11. 11.
    George G, Atallah E, Mauro M et al. Patients’ perspectives on the definition of cure in chronic myeloid leukemia: a US based survey. Accepted for ESH John Goldman Conference on CML, Sep 2018 (abstract).Google Scholar
  12. 12.
    Ritchie EK, Wolff JE, Latremouille-Viau D, et al. Tyrosine kinase inhibitor (TKI) therapy discontinuation in patients with CML in chronic phase: a US clinical practice perspective. J Clin Oncol. 2017;35(15):7052 (abstract).CrossRefGoogle Scholar
  13. 13.
    • Abboud C, Berman E, Cohen A, et al. 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(22):4439–42.  https://doi.org/10.1182/blood-2013-03-490003 Highlights the importance of the financial burden of TKI therapy.CrossRefPubMedCentralGoogle Scholar
  14. 14.
    Winn AN, Keating NL, Dusetzina SB. Factors associated with tyrosine kinase inhibitor initiation and adherence among Medicare beneficiaries with chronic myeloid leukemia. J Clin Oncol. 2016;34(36):4323–8.  https://doi.org/10.1200/JCO.2016.67.4184.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Padula WV, Larson RA, Dusetzina SB et al. Cost-effectiveness of tyrosine kinase inhibitor treatment strategies for chronic myeloid leukemia in chronic phase after generic entry of imatinib in the United States. J Natl Cancer Inst. 2016;108(7). doi:  https://doi.org/10.1093/jnci/djw003
  16. 16.
  17. 17.
    Hochhaus A, Masszi T, Giles FJ, Radich JP, Ross DM, Gomez Casares MT, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31(7):1525–31.  https://doi.org/10.1038/leu.2017.63.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Mahon FX, Boquimpani C, Kim DW, Benyamini N, Clementino NCD, Shuvaev V, et al. Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase: results from a single-group, phase 2, Open-Label Study. Ann Intern Med. 2018;168(7):461–70.  https://doi.org/10.7326/M17-1094.CrossRefPubMedGoogle Scholar
  19. 19.
    Ritchie EK, Catchatourian R, Klisovic RB, Pinilla-Ibarz J, Deininger MW, Erba HP, et al. ENESTgoal treatment-free remission study: updated preliminary results and digital polymerase chain reaction analysis in patients with chronic myeloid leukemia in chronic phase who switched from imatinib to nilotinib. Blood. 2016;128(22):3090 (abstract).Google Scholar
  20. 20.
    Shah NP, Paquette R, Müller MC, Saussele S, Garcìa-Gutiérrez V, Jiménez-Velasco A, et al. Treatment-free remission (TFR) in patients with chronic phase chronic myeloid leukemia (CML-CP) and in stable deep molecular response (DMR) to dasatinib—the Dasfree study. Blood. 2016;128(22):1895 (abstract).Google Scholar
  21. 21.
    • Atallah E, Schiffer CA, Weinfurt KP, et al. Design and rationale for the life after stopping tyrosine kinase inhibitors (LAST) study, a prospective, single-group longitudinal study in patients with chronic myeloid leukemia. BMC Cancer. 2018;18(1):359.  https://doi.org/10.1186/s12885-018-4273-1 An important prospective study from US looking at various aspects of TKI cessation.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Atallah E, Schiffer CA, Radich JP, Weinfurt K, Zhang MJ, Kota K, et al. Results from the U.S. Life after Stopping TKIs (LAST) Study. Blood. 2017;130(s1):2903 (abstract).Google Scholar
  23. 23.
    Sweet KL, Hazlehurst L, Sahakian E, et al. A phase I study of ruxolitinib plus nilotinib in chronic phase CML patients with molecular evidence of disease. Blood. 2016;128(22):1892 (abstract).Google Scholar
  24. 24.
    Carter BZ, Mak PY, Mu H, et al. Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells. Sci Transl Med. 2016;8(355):355ra117.  https://doi.org/10.1126/scitranslmed.aag1180.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Hematology/OncologyMedical College of WisconsinMilwaukeeUSA

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