Molecular responses at 3 and 6 months after switching to a second-generation tyrosine kinase inhibitor are complementary and predictive of long-term outcomes in patients with chronic myeloid leukemia who fail imatinib

Leuk Lymphoma. 2015 Jun;56(6):1787-92. doi: 10.3109/10428194.2014.974047. Epub 2014 Nov 20.

Abstract

Early molecular response (MR) defined by BCR-ABL(IS) levels has prognostic impact in chronic myeloid leukemia (CML). MR was evaluated at 3 and 6 months after switching to nilotinib or dasatinib in 115 patients with resistance to imatinib. Three groups were delineated at 3 months (< 1%, 1-10% or > 10% BCR-ABL(IS) levels) with different outcomes at 3 years regarding major molecular response (MMR, 91%, 47%, 22%, p < 0.001), failure-free survival (FFS), progression-free survival (PFS, 96%, 89% and 78%, p = 0.05) and overall survival (OS). After 6 months, patients with MR < 1% had higher 3-year MMR (83% vs. 16%, p < 0.001), FFS, PFS (94% vs. 84%, p = 0.05) and OS. Four patients had 3-month and 6-month MR > 10% and < 1%, respectively (3-year FFS 50%). Thirteen had 3-month and 6-month MR < 10% and ≥ 1%, respectively (3-year FFS 38%). These findings confirm the strong predictive value of 3-month and 6-month BCR-ABL(IS) levels in imatinib-resistant patients.

Keywords: Chronic myeloid leukemia; early molecular response; predictive factor; tyrosine kinase inhibitor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Dasatinib / therapeutic use
  • Female
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use
  • Survival Analysis
  • Time Factors
  • Transcription, Genetic / drug effects
  • Treatment Failure
  • Treatment Outcome
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • nilotinib
  • Dasatinib