Early BCR-ABL1 decline in imatinib-treated patients with chronic myeloid leukemia: results from a multicenter study of the Chinese CML alliance

Blood Cancer J. 2018 Jun 15;8(7):61. doi: 10.1038/s41408-018-0093-4.

Abstract

An early molecular response is spectacularly predictive of outcome in chronic myeloid leukemia (CML) and early response landmarks may identify the high-risk patients likely to be benefit from an early therapy switch. In this study, we evaluated the most relevant cutoffs for early molecular response markers (BCR-ABL1 values at 3 months, log reduction and halving time between diagnosis and 3 months) in 476 first-line imatinib-treated Chinese patients with chronic phase CML. All outcomes were significantly superior for the 324 patients with 3-month BCR-ABL1 ≤10%, so did for the 270 patients with BCR-ABL1 >0.61 log reduction. BCR-ABL1 halving time ≤22 days was identified for patients with the most favorable outcome. Moreover, the prognosis was significantly poorest for patients with both halving time >44 days and BCR-ABL1 >10%. Importantly, multivariate regression analysis demonstrated that a BCR-ABL1 log reduction calculated at 3 months of 0.61 was the only variable that significantly predicted for OS. Our results highlight the importance of rapid initial decline of BCR-ABL1 in predicting satisfactory outcome. Our data support the evidence that monitoring BCR-ABL1 values at an early time point could contribute to accurately assess response and ultimately guide clinical decisions regarding the timing of therapeutic intervention.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression Regulation, Leukemic
  • 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 / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Survival Analysis
  • Transcription, Genetic
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • BCR-ABL1 fusion protein, human
  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl