title: Imatinib and pegylated IFN-α2b discontinuation in first-line chronic myeloid leukemia patients following a major molecular response.
abstract: OBJECTIVE
  Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-α2b) and imatinib may increase the rate of successful discontinuation.
  
  
  METHODS
  In this pilot study, we prospectively stopped imatinib from patients (n = 12) who had achieved major molecular response (MMR) after ≥12 months of treatment with either imatinib or imatinib+Peg-IFN-α2b. Molecular monitoring was carried out monthly for BCR-ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed.
  
  
  RESULTS
  In the monotherapy group, 5/6 patients lost MMR within 4 months. One patient remains to date in MR(4.0) 61 months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4 months while still receiving Peg-IFN-α2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3 months. One patient is still in sustained MR(4.0) at 58 months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells.
  
  
  CONCLUSIONS
  A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2 yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies.
authors.affiliation: Hematology Research Unit Helsinki, Department of Medicine, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Perttu
authors.initials: P
authors.lastname: Koskenvesa
authors.forename: Anna
authors.initials: A
authors.lastname: Kreutzman
authors.forename: Peter
authors.initials: P
authors.lastname: Rohon
authors.forename: Markus
authors.initials: M
authors.lastname: Pihlman
authors.forename: Emmi
authors.initials: E
authors.lastname: Vakkila
authors.forename: Anu
authors.initials: A
authors.lastname: Räsänen
authors.forename: Mirja
authors.initials: M
authors.lastname: Vapaatalo
authors.forename: Kari
authors.initials: K
authors.lastname: Remes
authors.forename: Tuija
authors.initials: T
authors.lastname: Lundán
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.forename: Jukka
authors.initials: J
authors.lastname: Vakkila
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D001549:Benzamides / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C417083:peginterferon alfa-2b
keywords: chronic myeloid leukemia; immune system; interferon; therapy discontinuation; tyrosine kinase inhibitor