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Minimal residual disease or cure in MPNs? Rationales and perspectives on combination therapy with interferon-alpha2 and ruxolitinib

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INTRODUCTION: The therapeutic landscape of the Philadelphia-negative myeloproliferative neoplasms (MPNs) is markedly changing consequent to the development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with myelofibrosis (MF) and patients with polycythemia vera (PV) who develop refractoriness or intolerance to hydroxyurea. The use of Interferon-alpha2 (IFN) is rapidly expanding in several countries, based upon favourable safety and efficacy profiles in several single-arm studies during the last 30 years, displaying complete hematological remissions in a large proportion of patients, a reduction in the JAK2V617 F and CALR mutational burden and in a subset of patients with PV with normalisation of the bone marrow after long-term treatment - even being sustained for several years after discontinuation of IFN. To this end the concept of chronic inflammation as the driving force for MPN disease progression is being increasingly recognized. This novel concept has initiated phase II studies in patients with PV and MF of combination therapy with IFN and RUX. Areas covered and Expert commentary: Herein we highlight the background, the rationales and perspectives for this novel combinatorial approach which is foreseen as the most encouraging and promising treatment for patients with MPNs - hopefully with the potential of cure - at least operational cure - in a subset of patients.

Original languageEnglish
JournalExpert Review of Hematology
Volume10
Issue number5
Pages (from-to)393-404
Number of pages12
ISSN1747-4094
DOIs
Publication statusPublished - May 2017

    Research areas

  • Amino Acid Substitution, Calreticulin, Clinical Trials, Phase II as Topic, Drug Therapy, Combination, Humans, Interferon-alpha, Janus Kinase 2, Mutation, Missense, Polycythemia Vera, Primary Myelofibrosis, Pyrazoles, Recombinant Proteins, Remission Induction, Journal Article, Review

ID: 52411198