Molecular monitoring in CML: how deep? How often? How should it influence therapy?

Blood. 2018 Nov 15;132(20):2125-2133. doi: 10.1182/blood-2018-05-848630.

Abstract

With the advent of tyrosine kinase inhibitors (TKIs), the goals of therapy in chronic myeloid leukemia (CML) are steadily shifting. Long-term disease control on TKI therapy has been the goal and expectation for most patients. More recently, treatment-free remission (TFR) has entered mainstream practice and is increasingly being adopted as the main goal of therapy. This therapeutic shift not only influences TKI selection but also, has necessitated the refinement and dissemination of highly sensitive and accurate molecular monitoring techniques. Measurement of BCR-ABL1 messenger RNA expression through reverse transcription quantitative polymerase chain reaction, reported according to the International Scale, has become the primary tool for response assessment in CML. Achieving specific time-dependent molecular milestones, as defined by global therapeutic guidelines, has been established as critical in maximizing optimal outcomes while identifying patients at risk of therapy failure. Depth and duration of a deep molecular response have become the new therapeutic targets in patients considered for TFR. Consequently, molecular monitoring in CML has become even more critical to ongoing response assessment, identifying patients with TKI resistance and poor drug adherence, and enabling TFR to be attempted safely and effectively.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Drug Monitoring / methods
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • RNA, Messenger / genetics*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Fusion Proteins, bcr-abl