title: Imatinib discontinuation in chronic phase myeloid leukaemia patients in sustained complete molecular response: a randomised trial of the Dutch-Belgian Cooperative Trial for Haemato-Oncology (HOVON).
abstract: BACKGROUND
  Tyrosine kinase inhibitors treatment in responding chronic myeloid leukaemia (CML) patients is generally continued indefinitely. In this randomised phase II trial, we investigated whether CML patients in molecular response(4.5) (MR(4.5), quantitative reverse-transcription polymerase chain reaction (RQ-PCR)) after previous combination therapy with imatinib and cytarabine may discontinue imatinib treatment safely.
  
  
  METHODS
  Thirty-three patients from the HOVON 51 study with an MR(4.5) for at least 2 years who were still on imatinib treatment were randomised between continuation of imatinib (arm A, n=18) or discontinuation of imatinib (arm B, n=15).
  
  
  RESULTS
  After a median follow up of 36 months since randomisation, 3 patients (17%) in arm A and 10 patients (67%) in arm B had a molecular relapse. All 3 relapsing patients in arm A had also stopped imatinib after randomisation. All but one relapsing patient relapsed within 7 months after discontinuation of imatinib. The molecular relapse rate at 12 and 24 months after randomisation was 0% and 6% (arm A) and 53% and 67% (arm B) respectively. As-treated analysis revealed 56% and 61% relapses at 1 and 2 years since cessation in patients who discontinued imatinib, in contrast to 0% of patients who continued imatinib. All evaluable patients remained sensitive to imatinib after reinitiation and regained a molecular response.
  
  
  CONCLUSIONS
  Our data suggest that discontinuation of imatinib is safe in patients with durable MR(4.5).
authors.affiliation: Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: n.thielen@vumc.nl.
authors.forename: Noortje
authors.initials: N
authors.lastname: Thielen
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Gregor E G
authors.initials: GE
authors.lastname: Verhoef
authors.forename: Titia
authors.initials: T
authors.lastname: Gussinklo
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
authors.forename: Simon M G
authors.initials: SM
authors.lastname: Daenen
authors.forename: Wendy
authors.initials: W
authors.lastname: Deenik
authors.forename: Rien
authors.initials: R
authors.lastname: van Marwijk Kooy
authors.forename: Eefke
authors.initials: E
authors.lastname: Petersen
authors.forename: Willem M
authors.initials: WM
authors.lastname: Smit
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Valk
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Jeroen J W M
authors.initials: JJ
authors.lastname: Janssen
mesh_terms: D001530:Belgium; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009426:Netherlands; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Chronic myeloid leukaemia; Complete molecular response; Discontinuation; Imatinib