title: The clinical significance of achieving different levels of cytogenetic response in patients with chronic phase chronic myeloid leukemia after failure to front-line therapy: is complete cytogenetic response the only desirable endpoint?
abstract: Many patients with chronic myeloid leukemia who have failed initial therapy with a tyrosine kinase inhibitor achieve a cytogenetic response that is not complete (ie, partial or minor). This study analyzes the clinical benefit of such responses and identifies value in achieving such responses. Patients with less than complete cytogenetic response to second -line therapy or beyond should be considered to have benefit from therapy and the value of this considered in the context of which alternative options are available.
  
  
  BACKGROUND
  Complete cytogenetic response (CCyR) is the gold standard for response to therapy for patients with chronic myeloid leukemia (CML) because it is associated with a survival benefit. However, patients who have failed initial therapy with a tyrosine kinase inhibitor (TKI) frequently achieve only partial or minor cytogenetic responses. The clinical benefit of such responses is unclear.
  
  
  METHODS
  We analyzed the records of all 165 consecutive patients treated in clinical trials with TKI as second-line therapy or beyond after failure to prior imatinib therapy.
  
  
  RESULTS
  A CCyR was achieved with second-line TKI therapy or beyond in 52% of patients, whereas 7% achieved a partial cytogenetic response (PCyR), 14% a minor cytogenetic response (mCyR), 14% complete hematologic response (CHR) only, and 17% no response. The 3-year survival probability was 98% for those with CCyR, compared to 83% with PCyR, 83% for mCyR, 76% for CHR, and 71% for no response. Survival free from transformation rates at 3 years were 93%, 73%, 84%, 88%, and 0%, respectively.
  
  
  CONCLUSIONS
  CCyR is associated with the greatest survival benefit among patients treated with second-line therapy or beyond and remains the optimal cytogenetic goal of therapy. However, patients with partial and minor cytogenetic response derive a benefit compared to patients who have no response. This benefit should be recognized and evaluated against any alternative option available to a given patient before a change in therapy is recommended.
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, USA. jcortes@mdanderson.org
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintas-Cardama
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Burton
authors.forename: Jenny
authors.initials: J
authors.lastname: Shan
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002869:Chromosome Aberrations / Q000187:drug effects; D002871:Chromosome Banding; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors