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A phase 2 trial of decreasing tyrosine kinase inhibitor dose in chronic myeloid leukaemia patients with stable major molecular response: data from the British DESTINY study

Clark, Richard E.; Polydoros, Fotios; Apperley, Jane F.; Milojkovic, Dragana; Pocock, Christopher; Smith, Graeme; Byrne, Jenny L.; de Lavallade, Hugues; O'Brien, Stephen G.; Coffey, Tony; Foroni, Letizia; Copland, Mhairi

Authors

Richard E. Clark clarkre@liverpool.ac.uk.

Fotios Polydoros

Jane F. Apperley

Dragana Milojkovic

Christopher Pocock

Graeme Smith

Jenny L. Byrne jenny.byrne@nottingham.ac.uk

Hugues de Lavallade

Stephen G. O'Brien

Tony Coffey

Letizia Foroni

Mhairi Copland



Abstract

BACKGROUND: Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia (CML) with deep molecular responses, defined as stable MR4 (BCR-ABL1/ABL1 ratio 0.1%) on two consecutive samples. The study endpoint is the proportion of patients who lose their MMR on de-escalation and regain MMR on TKI resumption. The trial was registered at https://clinicaltrials.gov/ as NCT 01804985.
FINDINGS: During the 12 months of half-dose therapy, 12 patients had molecular recurrence, all of whom regained MMR within 4 months of full dose TKI resumption. Recurrence was lower in the MR4 cohort (3 of 121 evaluable patients; 2.5%, 90% CI: 0.2-4.8%) than in the MMR cohort (9 of 48 evaluable patients; 18.8%, 90% CI: 9.5-28%) (p = 0.0007), but was unrelated to prior TKI or TKI therapy duration. Many adverse events improved during the first 3 months of de-escalation, though not thereafter. Overall, de-escalation saved 46.7% from an expected TKI budget (without de-escalation) of £4,156,969.
INTERPRETATION: TKI de-escalation is safe for the vast majority of patients with excellent responses to TKI therapy, and is associated with improvement in symptoms and significant financial savings. The data imply that lower TKI doses may maintain responses in these patients.

Journal Article Type Article
Publication Date Jul 1, 2017
Journal Lancet Haematology
Electronic ISSN S2352-3026(17)30066-2
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 4
Issue 7
APA6 Citation Clark, R. E., Polydoros, F., Apperley, J. F., Milojkovic, D., Pocock, C., Smith, G., …Copland, M. (2017). A phase 2 trial of decreasing tyrosine kinase inhibitor dose in chronic myeloid leukaemia patients with stable major molecular response: data from the British DESTINY study. Lancet Haematology, 4(7), doi:10.1016/S2352-3026(17)30066-2
DOI https://doi.org/10.1016/S2352-3026%2817%2930066-2
Keywords chronic myeloid leukaemia, tyrosine kinase inhibitors, stopping treatment, imatinib, nilotinib, dasatinib
Publisher URL http://www.sciencedirect.com/science/article/pii/S2352302617300662?via%3Dihub
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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