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

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