Interferons in Polycythemia Vera Management

Dr Lucia Masarova discusses the place of interferons in the treatment of polycythemia vera, particularly in achieving hematological response and disease control​.

I would like to welcome you to this activity. The title is “Interferons in Polycythemia Vera Management.” My name is Lucia Masarova from MD Anderson Cancer Center, and it is a great pleasure to be here with you today. Interferons are biologic cytokines that have disease-modifying effects and potential for patients with myeloproliferative neoplasms. They have immunomodulatory and anti-inflammatory effect and have been used for myeloproliferative neoplasms for a couple of decades. The most common administrations of interferons for MPNs are subcutaneous. For patients with polycythemia vera, the goals of therapies have been shown to differ between patients and providers, where patients' most significant desires were to slow and delay the disease progression, improve symptoms, reduce the risk of thrombosis. For clinicians treating these patients, they included prevention of thrombotic or vascular events as the most significant risks. Patients with polycythemia vera goals of treatments are currently thrombotic management, so a patient that would be a high risk of thrombosis would be indicated for therapy, or patients that would be low-risk otherwise who have uncontrolled disease.

Interferons in patients with polycythemia vera make the most sense because it does combine the goals. We could decrease the risk of thrombosis, and we could offer something we call disease modification, because interferons predominantly target the malignant clones and are capable to reduce the allele burden of JAK2 V617F, which is the most common molecular marker of patients with polycythemia vera. Therefore, interferons could not only control thrombosis and block counts but also offer disease progression slowdown. Pegylated interferons have represented the mainstream of use in the last years for patients with polycythemia vera and are currently also recommended in the guidelines and represent a hallmark of the treatment landscape for high-risk patients with polycythemia vera as well as low-risk patients requiring therapies. The 2 most common interferons and standardly recommended are pegylated interferon alfa-2a and ropegylated interferon alfa-2b that exist for patients with polycythemia vera. When using interferons, we have to pay attention to safety and tolerability, which has historically remained central to the use of these agents.

So, whether you are using it as an initial therapy or switching from previous cytoreductive agents, which usually constitute hydroxyurea, I would encourage to significantly and closely monitor clinical and laboratory parameters to assure safe and effective therapies. Although pegylated interferon has now a more convenient dose—where the standard pegylated would be every week, the ropeginterferon every 2 weeks or every month—we still see side effects that could limit the clinical use. Therefore, they have to be closely monitored. We should start interferons with monitoring at the beginning and then every 3, 6 months. Also, every disease or every dose escalation should be monitored particularly for blood counts, chemistry, and because of the more significant autoimmune risk thyroid function tests as well as other as indicated. The dose is being titrated, which is more typically seen with ropeginterferon; however, also pegylated interferon until we achieve complete hematologic control with acceptable tolerance.

If patients cross to interferons from hydroxyurea, that should be gradually decreased. As interferons are up-titrated, hydroxyurea should be down-titrated and slowed down. This decision is based on the control of symptoms, blood counts, as well as tolerability. So, to summarize, interferons have clear and growing roles in patients with polycythemia vera. They do offer excellent control of blood counts, disease parameters. They are representing cytoreductive agents with also having a potential for disease modification and deeper targeting on JAK2 V617F, as well as bone marrow morphology. However, its use is tightly close to patient selection, safety profile, close monitoring, and gradual application as allowed per patient's tolerability and hematologic and symptoms control. Thank you very much for listening. This was, again, a talk on interferons in polycythemia vera management, and I will encourage you to take 1-question quiz after completing this video.