Low‐dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment‐free remission in chronic myeloid leukemia patients: Results of a retrospective study

Long‐term treatment‐free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). In clinical practice, tyrosine kinase inhibitor (TKI) dose reductions can be considered a means of preventing adverse effects and improving quality of life. We hypothesized that administration of low‐dose TKIs before treatment discontinuation does not impair TFR in patients with CML who have a deep molecular response (DMR, ≥MR4).

[1]  I. Glauche,et al.  Molecular monitoring during dose reduction predicts recurrence after TKI cessation in CML , 2020 .

[2]  I. Glauche,et al.  Molecular dynamics during reduction of TKI dose reliably identify molecular recurrence after treatment cessation in CML. , 2020, Blood.

[3]  E. Lengliné,et al.  Towards a Personalized Treatment of Patients with Chronic Myeloid Leukemia , 2019, Current Hematologic Malignancy Reports.

[4]  R. Clark.  Tyrosine Kinase Inhibitor Therapy Discontinuation for Patients with Chronic Myeloid Leukaemia in Clinical Practice , 2019, Current Hematologic Malignancy Reports.

[5]  J. Byrne,et al.  De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. , 2019, The Lancet. Haematology.

[6]  M. Copland.  Is There a Role for Dose Modification of TKI Therapy in CML? , 2019, Current Hematologic Malignancy Reports.

[7]  M. Baccarani,et al.  Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice , 2019, Haematologica.

[8]  I. Pivneva,et al.  Tyrosine kinase inhibitor therapy treatment and discontinuation in patients with chronic myeloid leukemia in chronic phase in the United States: a clinical practice perspective , 2019, Leukemia & lymphoma.

[9]  M. Konopleva,et al.  Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience , 2019, Journal of Hematology & Oncology.

[10]  M. Teixeira,et al.  Discontinuation of tyrosine kinase inhibitors in CML patients in real-world clinical practice at a single institution , 2018, BMC Cancer.

[11]  T. Brümmendorf,et al.  Efficacy and Safety Following Dose Reduction of Bosutinib or Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia: Analysis of the Phase 3 BFORE Trial , 2018, Blood.

[12]  F. Sánchez-Guijo,et al.  Feasibility of treatment discontinuation in chronic myeloid leukemia in clinical practice: results from a nationwide series of 236 patients , 2018, Blood Cancer Journal.

[13]  J. Radich,et al.  Chronic Myeloid Leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. , 2018, Journal of the National Comprehensive Cancer Network : JNCCN.

[14]  J. Cayuela,et al.  Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: Recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group , 2018, Cancer.

[15]  I. Glauche,et al.  Reduced tyrosine kinase inhibitor dose is predicted to be as effective as standard dose in chronic myeloid leukemia: a simulation study based on phase III trial data , 2018, Haematologica.

[16]  Martin C. Müller,et al.  Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. , 2018, The Lancet. Oncology.

[17]  X. Leleu,et al.  Sustained molecular response in chronic myeloid leukemia deep responders treated with low dose tyrosine kinase inhibitors , 2018, Leukemia & lymphoma.

[18]  F. Mahon.  Treatment-free remission in CML: who, how, and why? , 2017, Hematology. American Society of Hematology. Education Program.

[19]  T. Brümmendorf,et al.  Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants , 2017, Leukemia.

[20]  J. Byrne,et al.  De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. , 2017, The Lancet. Haematology.

[21]  H. Kantarjian,et al.  Impact of dose reductions on 5-year efficacy in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) from DASISION. , 2017 .

[22]  M. Tulliez,et al.  Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  L. Akard,et al.  Rationale and motivating factors for treatment-free remission in chronic myeloid leukemia , 2016, Leukemia & lymphoma.

[24]  Sukjoong Oh,et al.  Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study , 2016, Haematologica.

[25]  M. Baccarani,et al.  European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia , 2016, Leukemia.

[26]  Tomáš Adam,et al.  A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment , 2016, Leukemia & lymphoma.

[27]  S. Redaelli,et al.  Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study , 2015, American journal of hematology.

[28]  M. Baccarani,et al.  Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment , 2015, Blood Cancer Journal.

[29]  R. Hehlmann,et al.  Interferon alpha 2 maintenance therapy may enable high rates of treatment discontinuation in chronic myeloid leukemia , 2015, Leukemia.

[30]  J. Cayuela,et al.  Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Francisco Cervantes,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. , 2013, Blood.

[32]  Philippe Rousselot,et al.  Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. , 2010, The Lancet. Oncology.

[33]  Paul Metcalfe,et al.  Establishment of the first World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL mRNA. , 2010, Blood.

[34]  Z. Estrov,et al.  Long‐term follow‐up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic‐phase chronic myeloid leukemia , 2019, Cancer.