BCR-ABL1 transcript at 3 months predicts long-term outcomes following second generation tyrosine kinase inhibitor therapy in the patients with chronic myeloid leukaemia in chronic phase who failed Imatinib

Br J Haematol. 2013 Mar;160(5):630-9. doi: 10.1111/bjh.12187. Epub 2012 Dec 24.

Abstract

The BCR-ABL1 transcript level at 3 months can predict long-term outcomes following frontline therapy with Imatinib or Dasatinib in chronic myeloid leukaemia (CML) patients. However, data is lacking for second-generation tyrosine kinase inhibitor (2GTKI) therapy after Imatinib failure. A total of 112 patients with CML in chronic phase receiving 2GTKI after Imatinib failure were reviewed. Treatment outcomes including complete cytogenetic (CCyR), major molecular (MMR) and molecular response 4.5 (4.5 log reduction of BCR-ABL1 transcript level, MR(4.5) ), treatment failure, progression-free and overall survival (OS) were compared according to BCR-ABL1 transcript levels at 3 or 6 months, divided into <1%(IS) , 1-10%(IS) and ≥ 10%(IS) . BCR-ABL1 transcript level at 3 months showed better correlation with OS (P < 0.001) than that at 6 months (P = 0.147). Better OS was also observed in the patients achieving <1%(IS) (100%) and 1-10%(IS) (100%) than those with ≥ 10%(IS) at 3 months (70.6%, P < 0.001). Those with <1%(IS) showed the best CCyR, MMR and MR(4.5) rates; 1-10%(IS) , intermediate; and ≥ 10%(IS) , the lowest CCyR, MMR and MR(4.5) rates. The group with <1%(IS) at 3 months maintained significantly lower BCR-ABL1 transcript level compared to other two groups. In conclusion, the BCR-ABL1 transcript level at 3 months is the most relevant surrogate for outcomes following 2GTKI therapy after Imatinib failure.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor
  • Dasatinib
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Fusion Proteins, bcr-abl / biosynthesis
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Imatinib Mesylate
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / enzymology
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / classification
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / blood*
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / blood*
  • Remission Induction
  • Retrospective Studies
  • Thiazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • RNA, Messenger
  • RNA, Neoplasm
  • Thiazoles
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • nilotinib
  • Dasatinib