Discontinuation of tyrosine kinase inhibitors in CML patients in real-world clinical practice at a single institution

BMC Cancer. 2018 Dec 12;18(1):1245. doi: 10.1186/s12885-018-5167-y.

Abstract

Background: Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) will relapse if treatment is withdrawn, but various trials have recently demonstrated that a significant proportion of patients who achieved a stable and deep molecular response (DMR) can stop therapy without relapsing. However, most information on treatment cessation was obtained from clinical trials with strict recruiting criteria.

Methods: We evaluated the outcome of 25 patients with CML that discontinued TKI therapy in our institute in real-world clinical practice.

Results: Of the 25 patients, 76% discontinued therapy in sustained deep molecular response (SDMR) and 24% were in unsustained DMR (UDMR). Discontinuation of therapy due to adverse effects was observed in 5 and 50% of the patients in the SDMR and UDMR groups, respectively. After TKI discontinuation, patients were followed for a median of 24 months. At the time of this analysis, 56% patients had a molecular relapse after a median of 4 months. SDMR and longer treatment duration were associated with lower probability of molecular relapse: 25% in SDMR patients with TKI treatment > 96 months and 85% in UDMR patients with TKI treatment ≤96 months. All relapsed patients promptly resumed TKI therapy and regained at least major molecular response (MMR).

Conclusions: Our results suggest that TKI discontinuation is safe outside clinical trials and particularly effective in CML patients who are in SDMR with longer TKI treatment duration.

Keywords: Chronic myeloid leukemia; Sustained deep molecular response; TKI discontinuation; TKI therapy duration; Unsustained deep molecular response.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytogenetic Analysis / trends
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / administration & dosage*
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome
  • Withholding Treatment / trends*
  • Young Adult

Substances

  • Protein Kinase Inhibitors