title: Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia: what is the optimal response?
abstract: OBJECTIVE
  The response definitions proposed by the European LeukemiaNet (ELN) are defined on the basis of imatinib front-line therapy. It is unknown whether these definitions apply to patients treated with second-generation tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  One hundred sixty-seven patients with newly diagnosed chronic myelogenous leukemia (CML) in chronic phase were treated with second-generation TKIs in phase II trials (nilotinib, 81; dasatinib, 86). Median follow-up was 33 months. Event-free survival (EFS) was measured from the start of treatment to the date of loss of complete hematologic response, loss of complete or major cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, progression to accelerated or blastic phases, or death at any time.
  
  
  RESULTS
  Overall, 155 patients (93%) achieved complete cytogenetic response (CCyR), including 146 (87%) with major molecular response (MMR; complete in 46 patients [28%]). According to the ELN definitions, the rates of suboptimal response were 0%, 2%, 1%, and 12% at 3, 6, 12, and 18 months of therapy, respectively. There was no difference in EFS and CCyR duration between patients who achieved CCyR with and without MMR across all the landmark times of 3, 6, 12, and 18 months.
  
  
  CONCLUSIONS
  The use of second-generation TKIs as initial therapy in CML induces high rates of CCyR at early time points. The ELN definitions of response proposed for imatinib therapy are not applicable in this setting. We propose that achievement of CCyR and partial cytogenetic response at 3 months should be considered optimal and suboptimal responses, respectively. The achievement of MMR offered no advantage over CCyR in defining long-term outcome in patients with newly diagnosed CML treated with second-generation TKIs.
authors: University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX 77030, USA. ejabbour@mdanderson.org
authors: Elias
authors: E
authors: Jabbour
authors: Hagop M
authors: HM
authors: Kantarjian
authors: Susan
authors: S
authors: O'Brien
authors: Jianqin
authors: J
authors: Shan
authors: Alfonso
authors: A
authors: Quintás-Cardama
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: Mary Beth
authors: MB
authors: Rios
authors: Jorge E
authors: JE
authors: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases