Expert Discusses Evolution, Impact of Interferon in MPNs

Caroline Seymour
Published: Thursday, Feb 21, 2019
Srdan Verstovsek, MD, PhD

Srdan Verstovsek, MD, PhD

Limited research on interferon has prevented its widespread use in patients with myeloproliferative neoplasms (MPNs); however, newer generations of the treatment are demonstrating noninferiority to its favored counterpart, hydroxyurea, and are showing greater tolerability and efficacy compared with older generations of the agent, explained Srdan Verstovsek, MD, PhD.

“One needs to be selective in the patient population that is [receiving] interferon,” said Verstovsek. “Early evidence suggests that the long-acting and super long-acting interferon appears to be less toxic, even over a long period of time. This was not the case with earlier types of interferon that were given 3 or 5 times a week. The average duration of therapy was not too long, perhaps up to 5 years on average.”

With novel forms, that timespan may be prolonged, added Verstovsek. The ultimate goal is to give the therapy for decades, as patients with essential thrombocythemia (ET) or polycythemia (PV) live longer lives, close to a normal life expectancy.

In an interview with OncLive, Verstovsek, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms at The University of Texas MD Anderson Cancer Center, discussed the use of interferon in these rare blood diseases.

OncLive: Could you provide a history of the use of interferon in MPNs?

Verstovsek: Interferon is a biological product. We all have it in our body; it shows up when we have inflammation or infection. As such, it has been used in cancer therapy. It was discovered to be useful in patients with chronic diseases of the bone marrow. Interferon was standard of care in chronic myeloid leukemia (CML) until about 2001 because it would improve the bone marrow environment and decrease the number—sometimes even eliminate the number—of malignant cells in the bone marrow. Essentially, it would normalize the blood cell counts, thereby making some patients live longer. In CML, that was replaced by specific inhibitors in the early 2000s.

Interferon was also used in other MPNs, such as PV, ET, and sometimes, in myelofibrosis. In this setting, interferon was as effective as in CML, in normalizing the bone marrow and providing long-term control of the blood cell count. Some would even say that the long-term use of interferon in these conditions would prevent disease progression or eliminate the underlying malignant clone in some patients with CML, although that would be a rare success.

We began to use interferon in ET, PV, or myelofibrosis after developing a long-acting interferon that’s given once a week. Interferon is a biological protein, so it cannot be given by mouth; instead, it’s given by injection. Traditional interferon has been given by injection 3 to 5 times a week. The long-acting interferon is a slow release that can be given once a week.

Some of the newer [generations] that are being developed in Europe are given even less frequently—every 2 weeks or even once a month. That’s important because interferon does carry some toxicity; it may make people feel unwell, resulting in flu-like symptoms.

However, long-acting interferon appears to be decreasing the frequency of adverse events and increasing the tolerability and efficacy. That appears to be the case, especially with the most recent development of the super long-acting interferon in Europe called ropeginterferon.

That is certainly reflected in the higher efficacy and long-term efficacy [rates]. Durability is another issue. If you have an active agent that [remains active for a very long period of time], there are some toxicities that develop later in the course of the therapy, including autoimmune conditions or depression.

Could you discuss ropeginterferon and its potential in this space?

Ropeginterferon was recently approved in Europe; the announcement was made in December 2018 for the treatment of patients with PV. We hope that we will have that particular medication here in the United States, in clinical studies, in the very near future.

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