Treatment-Free Remission in CML: the US Perspective
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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.
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.
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.
KeywordsLeukemia Myeloid Chronic Treatment Discontinuation
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.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 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
- 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
- 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.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.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.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.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
- 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
- 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
- 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.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.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.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.• 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.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.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