Predictive value of early molecular response for deep molecular response in chronic phase of chronic myeloid leukemia

Medicine (Baltimore). 2019 Apr;98(15):e15222. doi: 10.1097/MD.0000000000015222.

Abstract

To investigate the association of 3- and 6-month BCR-ABL transcript levels on the international scale (BCR-ABL) and other factors with deep molecular response (DMR) achievement in chronic myeloid leukemia (CML)-chronic phase (CP) patients receiving tyrosine kinase inhibitor (TKI) therapy.We retrospectively analyzed the clinical data of 206 patients enrolled in our hospital between January 2010 and July 2018. These patients were initially diagnosed with CML-CP and received imatinib or nilotinib therapy. Early molecular response (EMR) was assessed based on BCR-ABL (IS: on the international scale) transcript level at 3 and 6 months. Potential factors impacting DMR achievement were identified using Cox proportional hazard regression models. The effects of EMR achievement on the cumulative incidence of MR4.0 were investigated via Kaplan-Meier analysis.Multivariate Cox regression analysis showed that a BCR-ABL transcript level at 3 and 6 months of TKI therapy was an independent factor for the achievement of MR4.0, which was nevertheless not related to age, gender, Sokal score, hemoglobin level, or white blood cell (WBC) count at the initial time of diagnosis. Patients achieving an EMR (EMR: 3-month BCR-ABL ≤10%, 6-month BCR-ABL <1%) were more likely to reach MR4.0 than patients failing to achieve EMR (P1 <.001, P2 <.001). Patients who had 3-month BCR-ABL ≤1% were more likely to reach MR4.0 than those who had 3-month BCR-ABL of 1% to 10% or >10% (P1 = .001, P2 <.001). Similarly, patients who had 6-month BCR-ABL ≤0.1% were more likely to achieve MR4.0 than those in the 0.1% to 1% and ≥1% groups (P1 <.001, P2 <.001). Also, a higher percentage of patients on nilotinib therapy achieved EMR compared with patients on imatinib therapy (93.3% vs 63.6% on 3-month nilotinib therapy, P = .001; 88.9% vs 59.9% on 6-month nilotinib therapy, P = .004).This study demonstrates that EMR, especially a 3-month BCR-ABL ≤1% and 6-month BCR-ABL ≤0.1%, have predictive value for DMR achievement. In addition, there is a higher percentage of patients receiving nilotinib therapy achieved EMR than that of those receiving imatinib therapy.

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Chronic Disease
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / therapeutic use
  • Retrospective Studies
  • Time Factors
  • Transcription, Genetic

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • nilotinib