title: Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a.
abstract: Pegylated interferon α-2a (PEG-IFN-α-2a) has previously been shown to induce hematologic and molecular responses in patients with polycythemia vera (PV) or essential thrombocythemia (ET). Here we present a follow-up of a phase 2 trial with PEG-IFN-α-2a treatment in 43 PV and 40 ET patients with detailed molecular analysis. After a median follow-up of 42 months, complete hematologic response was achieved in 76% of patients with PV and 77% of those with ET. This was accompanied by complete molecular response (CMR) (ie, undetectable JAK2V617F) in 18% and 17%, of PV and ET patients, respectively. Serial sequencing of TET2, ASXL1, EZH2, DNMT3A, and IDH1/2 revealed that patients failing to achieve CMR had a higher frequency of mutations outside the Janus kinase-signal transducer and activator of transcription pathway and were more likely to acquire new mutations during therapy. Patients with both JAK2V617F and TET2 mutations at therapy onset had a higher JAK2V617F mutant allele burden and a less significant reduction in JAK2V617F allele burden compared with JAK2 mutant/TET2 wild-type patients. These data demonstrate that PEG-IFN-α-2a induces sustained CMR in a subset of PV or ET patients, and that genotypic context may influence clinical and molecular response to PEG-IFN-α-2a.
authors.affiliation: Department of Leukemia, M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Wahab
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Outi
authors.initials: O
authors.lastname: Kilpivaara
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Roupie
authors.forename: Su-Jiang
authors.initials: SJ
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D044127:Epigenesis, Genetic; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000235:genetics* / Q000628:therapy; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000628:therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D049308:Dioxygenases; C541081:TET2 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C100416:peginterferon alfa-2a