title: Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase.
abstract: BACKGROUND
  The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined.
  
  
  METHODS
  The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard-dose (n = 73) or high-dose (n = 208) imatinib was investigated.
  
  
  RESULTS
  Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event-free survival (EFS) and transformation-free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose.
  
  
  CONCLUSIONS
  The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yesid
authors.initials: Y
authors.lastname: Alvarado
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate