Treatment of Philadelphia-positive chronic myeloid leukemia with imatinib: importance of a stable molecular response

Clin Cancer Res. 2009 Feb 1;15(3):1059-63. doi: 10.1158/1078-0432.CCR-08-1195.

Abstract

Purpose: The achievement of a major molecular response (MMolR) at 12 months is a surrogate marker of progression-free survival in chronic myeloid leukemia patients treated with imatinib.

Experimental design: We evaluated the prognostic value of the long-term evolution of the molecular response based on a retrospective analysis of 130 late chronic phase chronic myeloid leukemia patients who achieved a complete cytogenetic response (CCgR) with 400 mg/d imatinib and have now a median follow-up of 72 months (range, 48-77).

Results: In 71 (55%) patients, molecular response was consistently major (stable MMolR); in 19 (15%) patients, molecular response was occasionally less than major (unstable MMolR); in 40 (30%) patients, MMolR was never achieved (never MMolR) during all the course of CCgR. Patients with stable MMolR had a longer CCgR duration and a significantly better progression-free survival compared with patients with absent or unstable MMolR. The achievement of a MMolR, if maintained continuously, conferred a marked long-term stability to the CCgR: patients with a stable MMolR have a significantly lower risk of losing the CCgR than patients with unstable and never MMolR (4% versus 21%, P = 0.03, and 4% versus 33%, P < 0.0001, respectively). Finally, if a MMolR is not maintained consistently, the risk of losing the CCgR is higher but not significantly than if it is never achieved (33% versus 21%, P = 0.5).

Conclusions: These data confirm that achieving a MMolR is prognostically important but point out that the prognostic value of achieving a MMolR is greater if the response is confirmed and stable.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Benzamides
  • Disease-Free Survival
  • Female
  • Fusion Proteins, bcr-abl / analysis*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myeloid, Chronic-Phase / drug therapy
  • Leukemia, Myeloid, Chronic-Phase / genetics*
  • Male
  • Middle Aged
  • Piperazines
  • Prognosis
  • Pyrimidines
  • Time Factors

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl