title: Outcome after failure of second generation tyrosine kinase inhibitors treatment as first-line therapy for patients with chronic myeloid leukemia.
abstract: BACKGROUND
  The outcome of patients with CML who discontinue 2G-TKI initial therapy is unknown. We analyzed the characteristics of patients in whom treatment with first-line 2G-TKIs had failed.
  
  
  METHODS
  A total of 218 patients with CML were treated with dasatinib (n = 101) or nilotinib (n = 117; 12 in AP). After a median follow-up of 23 months, 40 patients (18%) discontinued therapy: 25 initially treated with nilotinib (21% of all treated with nilotinib; 6 treated in AP) and 15 (15%) initially treated with dasatinib. Median age of the patients was 47 (range, 19-79) years, and they had received therapy for a median of 8 (range, 0-62) months.
  
  
  RESULTS
  Reasons for treatment discontinuation include: toxicity, 16 patients; resistance in CP, 5 patients; transformation to blast phase, 4 patients (2 treated in AP); and other reasons, 15 patients. Subsequent treatment was imatinib in 11 patients, nilotinib in 7, dasatinib in 4, ponatinib in 2, chemotherapy plus dasatinib in 3, stem cell transplant in 2, bafetinib in 1, and unknown or none in 8 patients. A complete cytogenetic response was achieved in 19 patients, including 17 with major molecular response. Fourteen of the patients who achieved a complete molecular response or major molecular response with subsequent TKIs were in CP at the time of 2G-TKI discontinuation.
  
  
  CONCLUSIONS
  We conclude that treatment failure after first-line therapy with 2G-TKIs is mostly associated with toxicity or patient preference, and these patients respond well to alternative TKIs.
authors.affiliation: Leukemia Department, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Eghtedar
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Burton
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintas-Cardama
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: CML; Dasatinib; Discontinuation; Nilotinib; TKIs