Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy

Cancer. 2012 Jun 15;118(12):3116-22. doi: 10.1002/cncr.26568. Epub 2012 Feb 27.

Abstract

Background: The long-term outcome of patients with chronic phase chronic myeloid leukemia treated with imatinib after failure of interferon alpha therapy has not been detailed.

Methods: In total, 368 patients were analyzed. Univariate and multivariate survival analyses were conducted using standard statistical methods.

Results: Overall, 247 patients (67%) achieved a complete cytogenetic response (CCyR). Of the 327 patients who were studied, 207 patients (63%) achieved a major molecular response (MMR), and 99 patients (30%) had undetectable breakpoint cluster region/c-abl oncogene (BCR-ABL) levels at some time during therapy. The estimated 10-year survival rate was 68%, the progression-free survival rate was 67%, and the event-free survival rate was 51%. In multivariate analysis, age ≥ 60 years, hemoglobin <10 g/dL, bone marrow basophils ≥ 5%, any peripheral blasts, and clonal evolution were independent adverse factors for survival. The estimated 7-year survival rate according to the presence of no factors (n = 154), 1 or 2 factors (n = 190), or ≥ 3 factors (n = 24) were 93%, 70%, and 25%, respectively (P < .01). Achieving an MMR, a CCyR, or a partial cytogenetic response at 12 months was associated with significantly better 10-year survival rate in a landmark analysis (10-year survival rate, 80%-90%) compared with achieving a minor cytogenetic response or a complete hematologic response (10-year survival rate, 55%-65%) or another response (10-year survival rate, 10%). In a landmark analysis that included imatinib response at 12 months, achieving a major cytogenetic response or better (hazard ratio, 0.12; P < .001) and achieving a complete hematologic response or a minor cytogenetic response (hazard ratio, 0.36; P = .003) were significant favorable prognostic factors.

Conclusions: The current results indicated that the estimated 10-year survival rate of 68% for patients with chronic myeloid leukemia who receive imatinib after failure on interferon has improved.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / drug effects
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • Interferon-alpha / therapeutic use*
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / mortality
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / administration & dosage*
  • Retreatment
  • Survival Rate
  • Treatment Failure
  • Treatment Outcome

Substances

  • Benzamides
  • Interferon-alpha
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl