Long term molecular responses in a cohort of Danish patients with essential thrombocythemia, polycythemia vera and myelofibrosis treated with recombinant interferon alpha

Leuk Res. 2013 Sep;37(9):1041-5. doi: 10.1016/j.leukres.2013.06.012. Epub 2013 Jul 1.

Abstract

Within recent years data has accumulated demonstrating the efficacy of recombinant interferon alpha2 (rIFN-alpha2) in the treatment of chronic myeloproliferative neoplasms (MPNs). We report on clinical and molecular data in the largest cohort of JAK2 V617F mutant MPN Danish patients (n=102) being treated long-term with rIFN-alpha2 (rIFN-alpha2a and rIFN-alpha2b in a non-clinical trial setting. The median follow-up was 42 months. We substantiate the capacity of rIFN-alpha2 to induce complete hematologic remissions (ET 95%, PV 68%) and molecular response. In total 76 patients (74.5%) had a decline in JAK2 V617F allele burden with a median reduction from baseline of 59% (95% c.i. 50-73%, range 3-99%). A decline in JAK2 V617F allele burden was recorded in both ET (median 24-10% (95% c.i.: 8-16%), and PV (median 59-35% (95% c.i.: 17-33%). Patients with the lowest pre-treatment JAK2 V617F allele burdens tend to achieve the most favourable responses on long term treatment with rIFN-alpha2. Eleven patients (10%) had deep molecular remissions with ≤ 2% JAK2 V617F mutant DNA. Finally, long term treatment with rIFN-alpha2 was associated with a very low thrombosis rate. Our observations are supportive of the concept of early up-front treatment with rIFN-alpha2.

Keywords: Interferon; JAK2; Molecular; Myeloproliferative.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Denmark
  • Female
  • Follow-Up Studies
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polycythemia Vera / drug therapy*
  • Polycythemia Vera / genetics
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / genetics
  • Prognosis
  • Recombinant Proteins / therapeutic use
  • Remission Induction
  • Retrospective Studies
  • Thrombocythemia, Essential / drug therapy*
  • Thrombocythemia, Essential / genetics
  • Time Factors
  • Young Adult

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • JAK2 protein, human
  • Janus Kinase 2