Use of Interferon Alfa in the Treatment of Myeloproliferative Neoplasms: Perspectives and Review of the Literature

Abstract

Interferon alfa was first used in the treatment of myeloproliferative neoplasms (MPNs) over 30 years ago. However, its initial use was hampered by its side effect profile and lack of official regulatory approval for MPN treatment. Recently, there has been renewed interest in the use of interferon in MPNs, given its potential disease-modifying effects, with associated molecular and histopathological responses. The development of pegylated formulations and, more recently, ropeginterferon alfa-2b has resulted in improved tolerability and further expansion of interferon’s use. We review the evolving clinical use of interferon in essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). We discuss interferon’s place in MPN treatment in the context of the most recent clinical trial results evaluating interferon and its pegylated formulations, and its role in special populations such as young and pregnant MPN patients. Interferon has re-emerged as an important option in MPN patients, with future studies seeking to re-establish its place in the existing treatment algorithm for MPN, and potentially expanding its use for novel indications and combination therapies.

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms

“…A major significance of Peg-IFNα-2a is its ability to target MPN stem cells and reduce mutant allele burden in MPN [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. Sustained molecular, haematological response and regression of BM fibrosis were seen in some patients after discontinuation of Peg-IFNα-2a, indicating the eradication of MPN stem cells [ 65 , 69 ] ( Table 2 ).…”

Advances in the Treatment of Polycythemia Vera: Trends in Disease Management

“…Another drawback of interferon use is the tedious dosing regimen (thrice weekly injections, approximately three million units per dose). Pegylated interferons were introduced to overcome this major disadvantage, and they also offer a better side effect profile [29]. Studies have shown that low-dose pegylated interferon alpha 2 has an even better efficacy when given in combination with ruxolitinib, characterized by improvement in cell counts and the bone marrow picture, reduced JAK2V617F mutation burden, and adequate amelioration of symptoms [30].…”

“…Studies have shown that low-dose pegylated interferon alpha 2 has an even better efficacy when given in combination with ruxolitinib, characterized by improvement in cell counts and the bone marrow picture, reduced JAK2V617F mutation burden, and adequate amelioration of symptoms [30]. The most commonly reported adverse effects with its use include malaise, myalgias, nausea, vomiting, and depressive episodes [29]. In an attempt to counteract these undesirable effects and retain the efficacy of this drug, a newer formulation has been devised, known as ropeginterferon alfa-2b.…”

“…Ropeginterferon alfa-2b is a novel interferon with an increased half-life, allowing for a simplified dosing regimen, a major limiting factor of traditional interferons [29]. It has an anti-proliferative effect on stem cells having the JAK2 mutation [31].…”

Metabolic Vulnerabilities and Epigenetic Dysregulation in Myeloproliferative Neoplasms

“…Among the current therapies, only allogenic stem cell transplantation is curative, capable of resolving bone marrow fibrosis and the malignant clone ( 28 ). Interferon-alpha is similarly promising, and while initially associated with treatment-limiting toxicities, the development of pegylated-interferon has made cytogenetic remission with this agent a real possibility ( 29 , 30 ). The JAK1/2 kinase inhibitor ruxolitinib was approved by the United States Food and Drug Administration in 2011 for high risk MF patients and in 2014 for certain PV patients ( 31 – 33 ).…”