Abstract
In the past few years, international treatment guidelines for chronic myeloid leukaemia have incorporated recommendations for attempting discontinuation of treatment with tyrosine-kinase inhibitors (TKIs) outside of the setting of a clinical trial with the aim of a treatment-free remission (TFR). Physicians involved in the treatment of chronic myeloid leukaemia need to be sufficiently well informed to guide patients through decision-making about the discontinuation of treatment with TKIs targeting BCR–ABL1 by providing a balanced assessment of the potential risks and benefits of stopping or continuing therapy. These guidelines also seek to ensure that the risks associated with being off treatment are kept to a minimum. In this Review, we summarize the clinical studies of TFR and how their results can guide routine clinical practice with a focus on specific aspects such as molecular monitoring and the pregnancy-specific risks associated with a TFR attempt in female patients. We also address the development of predictors of outcome after TKI discontinuation and present strategies that warrant further consideration to enable more patients to enter TFR.
Key points
Effective treatment with tyrosine-kinase inhibitors (TKIs) leads the majority of patients with chronic myeloid leukaemia to achieve a deep molecular response after ≥5 years of treatment.
Approximately 50% of patients with a sustained deep molecular response can discontinue the TKI and remain in treatment-free remission.
The availability of sensitive, standardized quantitative reverse transcriptase PCR to detect BCR–ABL1 mRNA in peripheral blood, with rapid follow-up of results, is an essential requirement before TKI discontinuation can be offered to patients.
Loss of a major molecular response (BCR–ABL1 mRNA > 0.1%) should trigger the resumption of TKI treatment and leads to restoration of a deep molecular response in >90% of patients.
The biological and clinical factors that influence the outcome after TKI discontinuation are under investigation, with possible predictors including duration of treatment and/or response, depth of molecular response and immunological factors.
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Acknowledgements
The authors receive financial support from the South Australian Cancer Council’s Beat Cancer Project on behalf of its donors and the State Government through the Department of Health. The authors are grateful to the many patients with chronic myeloid leukaemia who have participated in clinical studies and especially to the pioneers who participated in the earliest treatment-free remission studies. We also thank the many international colleagues whose research is cited here, and the scientific and clinical colleagues in Australia who have been instrumental to our own studies.
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D.M.R. receives research funding and honoraria from BMS and Novartis. T.P.H. receives research funding and honoraria from BMS and Novartis and is a member of the advisory board for BMS, Incyte and Novartis.
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Ross, D.M., Hughes, T.P. Treatment-free remission in patients with chronic myeloid leukaemia. Nat Rev Clin Oncol 17, 493–503 (2020). https://doi.org/10.1038/s41571-020-0367-1
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DOI: https://doi.org/10.1038/s41571-020-0367-1
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