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 »
« …Based on 30 years of experience with rIFN-α2 in the treatment of MPNs, showing the safety and efficacy and the recent marketing of the first rIFN-α2b formulation (Besremi) for use in the treatment of newly diagnosed PV patients, we can conclude that stem-cell- targeted therapy with rIFN-α2 will be the cornerstone in the future treatment of MPN patients. Unfortunately, a large number of patients do not tolerate rIFN-α2 or are refractory to treatment. The novel rIFN-α2b Besremi seems to be less toxic and perhaps also more effective than treatment with Pegasys, which is the only alternative today. Therefore, we are in an urgent need of stem-cell-targeting drugs other than Besremi and Pegasys, whether as monotherapies or in combination with agents that target the concurrent chronic inflammatory state, which is considered to be of major importance as the driving force for clonal expansion and evolution in the biological MPN continuum from early cancer stages (i.e., ET and PV) to the advanced myelofibrosis stage. Accordingly, studies on the safety and efficacy of pegylated IFN-β (e.g., Plegridy) are urgently needed, the optimal design being a randomized pilot study between pegylated rIFN-α2 (e.g., Pegasys or Besremi) and rIFN-β, with comparisons of safety, efficacy, and toxicity profiles and concurrent molecular and immune cell studies (i.e., frequencies, distribution, and functionality) before and during treatment. Studies of the safety and efficacy of rIFN-β in patients who are refractory or intolerant to rIFN-α2 might be highly important to determine whether rIFN-β might “rescue“ such patients. Studies of rIFN-β in the CHIP-JAK2V617F stage before the overt development of MPNs might also be highly relevant to assess whether rIFN-α2 or rIFN-β might reduce or potentially eradicate the malignant clone in the earliest stages of MPN development [54]. If studies of monotherapy with rIFN-β show similar or even superior safety and efficacy as compared to Besremi or Pegasys, the path is open for studies of the safety and efficacy of the combination therapies mentioned above, and possibly others as well (e.g., hydroxyurea, statins, and colchicine) [54]. Studies on the safety and efficacy of anti-CALR monoclonal antibody therapy are in the pipeline; as part of this research program, it might be tempting to conjugate with rIFN-α2 or rIFN-β. This strategy has been considered for years but has only recently been accomplished in the treatment of multiple myeloma. Lastly, in the COVID-19 era, it is important to underscore that several studies have shown rIFN-β to have a favorable impact on the clinical course of COVID-19. The rationales and evidence for using rIFN-β as monotherapy or in combination with ruxolitinib have most recently been thoroughly described… »
Interferon and the liver
