Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis

Stine Ulrik Mikkelsen, Lasse Kjær, Mads Emil Bjørn, Trine Alma Knudsen, Anders Lindholm Sørensen, Christen Bertel Lykkegaard Andersen, Ole Weis Bjerrum, Nana Brochmann, Daniel El Fassi, Torben A. Kruse, Thomas Stauffer Larsen, Hans Torben Mourits-Andersen, Claus Henrik Nielsen, Niels Pallisgaard, Mads Thomassen, Vibe Skov, Hans Carl Hasselbalch*

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


Interferon-α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation-mediated toxicity, leading to treatment discontinuation in 10-30% of patients. Ruxolitinib, a potent anti-inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon-α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon-α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low-/intermediate-1-risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon-α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow-up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty-seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon-α2 and ruxolitinib is efficacious in patients with low-/intermediate-1-risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients.

TidsskriftCancer Medicine
Udgave nummer8
Sider (fra-til)3571-3581
Antal sider11
StatusUdgivet - aug. 2018
Udgivet eksterntJa


  • combination therapy
  • interferon-alpha
  • myeloproliferative neoplasms
  • polycythemia vera
  • primary myelofibrosis
  • ruxolitinib

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