The Outcomes of Chronic Myeloid Leukemia Patients With Molecular Warning Responses During Imatinib Treatment According to the European LeukemiaNet 2013 Recommendations

Clin Lymphoma Myeloma Leuk. 2019 Jul;19(7):e377-e384. doi: 10.1016/j.clml.2019.03.028. Epub 2019 Apr 4.

Abstract

Background: In the European LeukemiaNet (ELN) 2013 recommendations, chronic myeloid leukemia (CML) patients with warning response (WR) were suggested to be monitored closely continuing with the same tyrosine kinase inhibitor (TKI). Differently, the guidelines of the National Comprehensive Cancer Network considers switching to another TKI as an option.

Patients and methods: We retrospectively evaluated 73 CML patients receiving first-line imatinib, who were followed and managed in accordance with ELN recommendations. We compared patients with molecular WR with patients with optimal response (OR) and failure regarding short- and long-term outcomes.

Results: The cumulative major molecular response (MMR) rates in patients with OR were significantly higher at any time point than those achieved by the WR group. Patients with WR at 3 months had significantly inferior failure-free survival (FFS) than optimal responders, but overall survival (OS) was similar. For 6 and 12 months, the WR and OR groups had similar FFS and OS. Twenty of 23 patients with WR at 12 months achieved MMR during imatinib treatment.

Conclusion: It takes longer to get to ELN time points with imatinib than second-generation TKIs (2GTKIs). Treatment might fail in a small proportion of the patients with WR during imatinib treatment, but close and careful monitoring and timely switching to 2GTKIs might translate into favorable outcomes. Avoiding early switch to 2GTKIs would prevent patients from experiencing potential toxicities. There is still a need for prospective comparative studies (ie, continuing imatinib treatment vs. switching to 2GTKIs) in patients with WR, to justify the validity of this response category and to explore the benefit of treatment change in these patients.

Keywords: Chronic myeloid leukemia; European LeukemiaNet (ELN); Imatinib; Tyrosine kinase inhibitor; Warning.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Humans
  • Imatinib Mesylate / administration & dosage
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl