Minimal Residual Disease or Cure in MPNs? Rationales and perspectives on Combo Therapy with Interferon-alpha2 and Ruxolitinib

Dr Ruben Mesa
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Minimal Residual Disease or Cure in MPNs? Rationales and perspectives on Combo Therapy with Interferon-alpha2 and Ruxolitinib

Pegasys Jakafi combo for MPNs

This abstract is provided by Mads Emil Bjorn & Hans Carl Hasselbalch – Department of Hematology, Region Zealand, Roskilde, Denmark



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 Pegasys Jakafi combo for MPNs(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.

Here is the link back to the abstract – Unfortunately, the complete research paper is not freely available.

Publisher Comments:

My question is where is the United States in the study of this most important combo therapy?  Denmark is in Phase 2 clinical trials in PV and MF patients.  France is in Phase 2 trials studying this combo for MF.  A search of, our public database of clinical studies, turns up nothing for the U.S.  Some progressive MPN specialist in the U.S. will prescribe the combo therapy for aggressive PV and MF patients.  Only time will tell which U.S. hematologists will apply a logical, forward-thinking approach, utilizing the state of the art combo, under close supervision for patients who are not responding to Ruxolitinib or Pegasys interferon (IFN) therapy on its own or other treatment.  More of my opinion on this subject can be found in part 2 of this article published Janary 2017.  Considering our limited treatment options, it sure beats waiting for lengthy clinical trials and FDA approval which could take many years.

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