Recombinant Interferon-β in the Treatment of Polycythemia Vera and Related Neoplasms: Rationales and Perspectives

SIMPLE SUMMARY: The myeloproliferative neoplasms (MPNs) are chronic blood cancers characterized by elevated blood cell counts and, after decades, the development of bone marrow failure. Blood clots are common and contribute massively to the symptom burden. Treatment with interferon (IFN) alpha-2 normalizes elevated blood cell counts within weeks to months. This treatment has been used off-label over the last 30 years. Today, a novel interferon alpha-2b formulation (Besremi) is marketed for treatment of the MPN disease polycythemia vera. Another IFN formulation is interferon beta (IFN-β), which has been used for decades in the treatment of multiple sclerosis. Several studies have shown IFN-β to possess stronger anticancer capabilities than IFN alpha-2. However, only a few cancer trials have been conducted, none in patients with MPNs. In this paper, the rationales and perspectives for using IFN-β in patients with MPNs are described, and future research directions are outlined for investigating the safety and efficacy of IFN-β in MPNs. ABSTRACT: About 30 years ago, the first clinical trials of the safety and efficacy of recombinant interferon-α2 (rIFN-α2) were performed. Since then, several single-arm studies have shown rIFN-α2 to be a highly potent anticancer agent against several cancer types. Unfortunately, however, a high toxicity profile in early studies with rIFN-α2 -among other reasons likely due to the high dosages being used-disqualified rIFN-α2, which was accordingly replaced with competitive drugs that might at first glance look more attractive to clinicians. Later, pegylated IFN-α2a (Pegasys) and pegylated IFN-α2b (PegIntron) were introduced, which have since been reported to be better tolerated due to reduced toxicity. Today, treatment with rIFN-α2 is virtually outdated in non-hematological cancers, where other immunotherapies—e.g., immune-checkpoint inhibitors—are routinely used in several cancer types and are being intensively investigated in others, either as monotherapy or in combination with immunomodulatory agents, although only rarely in combination with rIFN-α2. Within the hematological malignancies, rIFN-α2 has been used off-label for decades in patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs)—i.e., essential thrombocythemia, polycythemia vera, and myelofibrosis—and in recent years rIFN-α2 has been revived with the marketing of ropeginterferon-α2b (Besremi) for the treatment of polycythemia vera patients. Additionally, rIFN-α2 has been revived for the treatment of chronic myelogenous leukemia in combination with tyrosine kinase inhibitors. Another rIFN formulation-recombinant interferon-β (rIFN-β)—has been used for decades in the treatment of multiple sclerosis but has never been studied as a potential agent to be used in patients with MPNs, although several studies and reviews have repeatedly described rIFN-β as an effective anticancer agent as well. In this paper, we describe the rationales and perspectives for launching studies on the safety and efficacy of rIFN-β in patients with MPNs.