Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience

J Hematol Oncol. 2019 Jan 3;12(1):1. doi: 10.1186/s13045-018-0686-1.

Abstract

Background: Patients with CML treated with TKI can have a life expectancy comparable to that of the general population. Due to the extended duration of TKI administration, treatment discontinuation has been increasingly sought.

Methods: Medical records of 100 patients with CML who were in MR4.5 and discontinued their TKI outside clinical trials were reviewed.

Results: After a median follow-up of 30 months (range, 5-112 months) after discontinuation, 35% and 17% lost MR4.5 and major molecular response (MMR), respectively. Only six patients lost MMR 12 months or more after discontinuation. Loss of MR4.5 was observed in 29% and 7% of patients with sustained MR4.5 duration of more than 2 and 6 years before discontinuation, respectively. By univariate analysis, there was a higher risk of loss of MR4.5 for patients who were treated for less than 87 months, received second or subsequent line TKI, never received interferon, or those with sustained MR4.5 for less than 6 years. By multivariate analysis, sustained MR4.5 for 6 years or more was the only significant predictor for durable response. Overall, 30% of patients who discontinued while in MR4.5 were retreated with 93% regaining MR4.5 at a median of 5 months.

Conclusion: These results demonstrate that under proper conditions, treatment discontinuation is feasible outside of clinical trial setting. MR4.5 duration of 6 years or more before discontinuation is associated with very low risk of loss of MR4.5.

Keywords: CML; MR4.5; TKI discontinuation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / analysis
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Patient Dropouts*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Recurrence
  • Retreatment
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl