Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a

• Published in: Blood 2013-08, Vol.122 (6), p.893-901
• Main Authors: Quintás-Cardama, Alfonso, Abdel-Wahab, Omar, Manshouri, Taghi, Kilpivaara, Outi, Cortes, Jorge, Roupie, Anne-Laure, Zhang, Su-Jiang, Harris, David, Estrov, Zeev, Kantarjian, Hagop, Levine, Ross L., Verstovsek, Srdan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Clinical Trials and Observations; DNA Mutational Analysis; DNA-Binding Proteins - genetics; Epigenesis, Genetic; Female; Follow-Up Studies; Genotype; Humans; Interferon-alpha - therapeutic use; Janus Kinase 2 - genetics; Male; Middle Aged; Polycythemia Vera - genetics; Polycythemia Vera - therapy; Polyethylene Glycols - therapeutic use; Prospective Studies; Proto-Oncogene Proteins - genetics; Recombinant Proteins - therapeutic use; Remission Induction; Thrombocythemia, Essential - genetics; Thrombocythemia, Essential - therapy; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-07-442012

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. •Treatment with PEG-IFN-α-2a in PV and ET results in a high rate of complete hematologic and molecular responses.•Patients failing to achieve complete molecular remission tended to have higher frequencies of mutations in genes other than JAK2.