Minimal residual disease or cure in MPNs? Rationales and perspectives on combination therapy with interferon-alpha2 and ruxolitinib
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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Minimal residual disease or cure in MPNs? Rationales and perspectives on combination therapy with interferon-alpha2 and ruxolitinib. / Bjørn, Mads Emil; Hasselbalch, Hans Carl.
I: Expert Review of Hematology, Bind 10, Nr. 5, 2017, s. 393-404.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - Minimal residual disease or cure in MPNs?
T2 - Rationales and perspectives on combination therapy with interferon-alpha2 and ruxolitinib
AU - Bjørn, Mads Emil
AU - Hasselbalch, Hans Carl
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Amino Acid Substitution
KW - Calreticulin/genetics
KW - Clinical Trials, Phase II as Topic
KW - Drug Therapy, Combination/methods
KW - Humans
KW - Interferon-alpha/therapeutic use
KW - Janus Kinase 2/genetics
KW - Mutation, Missense
KW - Polycythemia Vera/drug therapy
KW - Primary Myelofibrosis/drug therapy
KW - Pyrazoles/therapeutic use
KW - Recombinant Proteins/therapeutic use
KW - Remission Induction
U2 - 10.1080/17474086.2017.1284583
DO - 10.1080/17474086.2017.1284583
M3 - Review
C2 - 28402197
VL - 10
SP - 393
EP - 404
JO - Expert Review of Hematology
JF - Expert Review of Hematology
SN - 1747-4086
IS - 5
ER -
ID: 195511292