Interferons in the treatment of myeloproliferative neoplasms.

ABSTRACT

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

A review of what interferons are and how they are used in the treatment of the myeloproliferative neoplasms polycythemia vera, essential thrombocythemia, and primary myelofibrosis Why was this paper written? This paper was written to summarize the current clinical landscape of the use of interferons for the treatment of myeloproliferative neoplasms (MPN). What are interferons and how are they used in MPNs? Interferons are small proteins involved in cellular signaling that have been used to treat MPNs, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), for more than 35 years. They can have modulatory effects on the immune system and on the fundamental causes of disease. The use of interferons as treatment was initially limited due to difficulties with their administration and the potential for significant adverse effects. Many of these shortcomings were addressed by chemically binding a biocompatible polymer, polyethylene glycol (PEG), to the structure of the interferon, which increases the stability of the protein, prolongs the time during which it is active, and reduces negative effects to the immune system. The combined chemical structure of PEG and interferon (pegylated interferon or peginterferon) is recommended for use in the treatment of PV, ET, and PMF. What topics are discussed in this paper? In this review paper we evaluate the clinical effectiveness and safety of two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi) and discuss the practical clinical management of interferon-based therapies, along with the authors' opinions on whether to and how to switch therapy from hydroxyurea. Key topics and questions related to the use of interferons, such as their safety and tolerability, the significance of their effects on mutated cells, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. What do the findings mean? Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.