title: Second-generation tyrosine kinase inhibitors improve the survival of patients with chronic myeloid leukemia in whom imatinib therapy has failed.
abstract: BACKGROUND
  It has not been clearly established whether second-generation tyrosine kinase inhibitors actually improve the survival of patients with chronic myeloid leukemia in chronic phase who are given nilotinib or dasatinib therapy after treatment failure with imatinib.
  
  
  METHODS
  To address this issue we compared the survival of 104 patients in whom first-line therapy with imatinib failed and who were then treated with second-generation tyrosine kinase inhibitors with the outcome of 246 patients in whom interferon-α therapy failed and who did not receive tyrosine kinase inhibitor therapy.
  
  
  RESULTS
  Patients treated with second-generation tyrosine kinase inhibitors had longer overall survival than the interferon controls (adjusted relative risk= 0.28, P=0.0001). However this survival advantage was limited to the 64.4% of patients in whom imatinib failed but who achieved complete cytogenetic response with the subsequent tyrosine kinase inhibitor (adjusted relative risk =0.05, P=0.003), whereas the 35.6% of patients who failed to achieve complete cytogenetic response on the second or third inhibitor had similar overall survival to that of the controls (adjusted relative risk=0.76, P=0.65).
  
  
  CONCLUSIONS
  Patients in whom imatinib treatment fails who receive sequential therapy with second-generation tyrosine kinase inhibitors have an enormous advantage in survival over controls (palliative therapy); this advantage is, however, limited to the majority of the patients who achieve a complete cytogenetic response.
authors.affiliation: Department of Haematology, Imperial College London, London, UK.
authors.forename: Amr R
authors.initials: AR
authors.lastname: Ibrahim
authors.forename: Richard E
authors.initials: RE
authors.lastname: Clark
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
authors.forename: Jenny
authors.initials: J
authors.lastname: Byrne
authors.forename: Pat
authors.initials: P
authors.lastname: Shepherd
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Dragana
authors.initials: D
authors.lastname: Milojkovic
authors.forename: Richard
authors.initials: R
authors.lastname: Szydlo
authors.forename: John
authors.initials: J
authors.lastname: Goldman
authors.forename: David
authors.initials: D
authors.lastname: Marin
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage; D001549:Benzamides; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate