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How I determine if and when to recommend stopping tyrosine kinase inhibitor treatment for chronic myeloid leukaemia
Author(s) -
Ross David M.,
Hughes Timothy P.
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12892
Subject(s) - imatinib , discontinuation , medicine , tyrosine kinase , chronic myeloid leukaemia , tyrosine kinase inhibitor , minimal residual disease , imatinib mesylate , oncology , drug holiday , immunology , myeloid leukemia , bone marrow , receptor , human immunodeficiency virus (hiv) , cancer
Summary Treatment‐free remission ( TFR ) has recently emerged as a goal of treatment in chronic myeloid leukaemia ( CML ). Molecular remission is sustained in around 30% of imatinib‐treated patients who stop treatment after ≥2 years with undetectable minimal residual disease ( UMRD ) by conventional real‐time reverse transcription polymerase chain reaction. An additional 20–30% of patients will lose UMRD , but remain in stable major molecular remission off treatment. Most patients with molecular recurrence have a significant increase in BCR ‐ ABL 1 within the first 6 months off treatment, but there are also rare late relapses. As re‐treatment with imatinib restores control, a trial of TFR is safe so long as careful molecular monitoring is provided to enable prompt re‐treatment. The minimum eligibility criteria for a trial of TFR are not yet defined, but the available data support a MRD level of around a molecular response of 4·5 log for at least 2 years. Factors associated with a higher probability of TFR include low risk Sokal score, prior interferon treatment, longer total duration of imatinib treatment and higher numbers of natural killer cells at the time of imatinib discontinuation. Preliminary data suggest that the rate of TFR in patients treated with more potent tyrosine kinase inhibitors will probably be higher. The biology that underlies TFR is an area of active investigation.