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.

Keywords: JAK2; essential thrombocythemia; interferon; myelofibrosis; myeloproliferative neoplasms; pegylated interferon; polycythemia vera; ropeginterferon alfa-2b.

Figure 1.

Considerations when switching to interferons. (a) Dosing regimen for ropeginterferon alfa-2b-njft (every 2 weeks) and peginterferon alfa-2a (every week). Peginterferon alfa-2a should be administered 45–90 μg subcutaneously weekly and titrated monthly in 45 μg increments to a maximum of 180 μg weekly. (Note that if there are concerns about sensitivity, even lower dosing can be considered.) The recommended starting dose of ropeginterferon alfa-2b-njft is 100 μg subcutaneously every 2 weeks (50 μg if receiving HU) with up-titration by 50 μg every 2 weeks to a maximum of 500 μg. After 1 year of treatment with ropeginterferon alfa-2b-njft and with hematological stability, dosing can be reduced to every 4 weeks. After 5 years, or even earlier, dosing of peginterferon alfa-2a can be adjusted to every 2 weeks. (b) Representative schematic of the titration regimens when switching a patient from HU to interferon, showing the concurrent titration up of interferon while titrating HU down. For those on HU prior to initiating ropeginterferon alfa-2b-njft, taper the HU off by reducing the total biweekly HU dose by 20–40% every 2 weeks during weeks 3–12 with complete discontinuation of HU by week 13. Interferon dose should be titrated up to the dose at which adequate hematologic results are obtained (maximum doses, peginterferon alfa-2a: 180 µg subcutaneously every week; ropeginterferon alfa-2b-njft: 500 µg subcutaneously every other week). ALC, absolute lymphocyte count; ALT, alanine transaminase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; CBC, complete blood count; Hb, hemoglobin; HU, hydroxyurea; IFN, interferon; PLT, platelet; T4, thyroxine; TSH, thyroid stimulating hormone; WBC, white blood cell.