title: Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera.
abstract: OBJECTIVE
  We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-alpha-2a) in patients with essential thrombocythemia (ET) and polycythemia vera (PV).
  
  
  METHODS
  Seventy-nine patients (40 with PV and 39 with ET) have been treated. Median time from diagnosis to PEG-IFN-alpha-2a was 54 months in patients with PV and 33 months in patients with ET. Eighty-one percent of patients had received prior therapy. The first three patients received PEG-IFN-alpha-2a at 450 microg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 microg weekly. Seventy-seven patients are evaluable and have been observed for a median of 21 months.
  
  
  RESULTS
  The overall hematologic response rate was 80% in PV and 81% in ET (complete in 70% and 76% of patients, respectively). The JAK2(V617F) mutation was detected in 18 patients with ET and 38 patients with PV; sequential measurements by a pyrosequencing assay were available in 16 patients with ET and 35 patients with PV. The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2(V617F)) in 6% and 14%, respectively. The JAK2(V617F) mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability of PEG-IFN-alpha-2a at 90 microg weekly was excellent.
  
  
  CONCLUSIONS
  PEG-IFN-alpha-2a resulted in remarkable clinical activity, high rates of molecular response, and acceptable toxicity in patients with advanced ET or PV. The ability of PEG-IFN-alpha-2a to induce complete molecular responses suggests selective targeting of the malignant clone.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Richie
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009503:Neutropenia / Q000139:chemically induced; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D013920:Thrombocythemia, Essential / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C100416:peginterferon alfa-2a