title: Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia.
abstract: Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg-IFN-α2b) 50 μg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
authors.affiliation: Department of Medical Sciences, University of Uppsala and Department of Hematology, University Hospital, Uppsala, Sweden. bengt.simonsson@medsci.uu.se
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Tobias
authors.initials: T
authors.lastname: Gedde-Dahl
authors.forename: Berit
authors.initials: B
authors.lastname: Markevärn
authors.forename: Kari
authors.initials: K
authors.lastname: Remes
authors.forename: Jesper
authors.initials: J
authors.lastname: Stentoft
authors.forename: Anders
authors.initials: A
authors.lastname: Almqvist
authors.forename: Mats
authors.initials: M
authors.lastname: Björeman
authors.forename: Max
authors.initials: M
authors.lastname: Flogegård
authors.forename: Perttu
authors.initials: P
authors.lastname: Koskenvesa
authors.forename: Anders
authors.initials: A
authors.lastname: Lindblom
authors.forename: Claes
authors.initials: C
authors.lastname: Malm
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
authors.forename: Kristina
authors.initials: K
authors.lastname: Myhr-Eriksson
authors.forename: Lotta
authors.initials: L
authors.lastname: Ohm
authors.forename: Anu
authors.initials: A
authors.lastname: Räsänen
authors.forename: Marjatta
authors.initials: M
authors.lastname: Sinisalo
authors.forename: Anders
authors.initials: A
authors.lastname: Själander
authors.forename: Ulla
authors.initials: U
authors.lastname: Strömberg
authors.forename: Ole Weiss
authors.initials: OW
authors.lastname: Bjerrum
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrencrona
authors.forename: Franz
authors.initials: F
authors.lastname: Gruber
authors.forename: Veli
authors.initials: V
authors.lastname: Kairisto
authors.forename: Karin
authors.initials: K
authors.lastname: Olsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Sandin
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Johan Lanng
authors.initials: JL
authors.lastname: Nielsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D015415:Biomarkers / Q000032:analysis; D054796:Drug Dosage Calculations; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction / Q000379:methods*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D015415:Biomarkers; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C100416:peginterferon alfa-2a