Pegylated Interferon Formulations Shake Up MPN Treatment

Caroline Seymour
Published: Monday, Feb 25, 2019
Abdulraheem Yacoub, MD
Abdulraheem Yacoub, MD
Due to the lack of comparative data between interferon and standard therapies, interferon has historically been reserved as a second-line therapy for patients with myeloproliferative neoplasms (MPNs). However, pegylated formulations, such as peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b (PEG-Intron), have demonstrated higher safety, efficacy, and tolerability profiles, explained Abdulraheem Yacoub, MD.

In the phase III MPN-RC 112 trial, findings of which were presented at the 2018 ASH Annual Meeting, patients with polycythemia vera (PV) or high-risk essential thrombocythemia (ET) were randomized to receive either pegylated interferon alfa-2a or standard hydroxyurea. Results from the final analysis revealed that, at 12 months and 24 months, complete response rates between the arms were comparable. Further, neither medication resulted in a compromised quality of life (QoL).

“Now, there is a trend to advocate for interferon use as first-line therapy in addition to patients who have already tried other therapeutic options,” said Yacoub. “For patients who have had issues with tolerance or resistance to standard drugs, interferon remains a very viable second-line option.”

In an interview with OncLive, Yacoub, associate professor of medicine at the University of Kansas Medical Center, discussed the development of interferon and its current role in the management of patients with MPNs.

OncLive: How long has interferon been part of the MPN treatment paradigm?

Yacoub: MPNs are rare blood cancers that were described many decades ago. Many therapeutic interventions have been planned and evaluated over the years. Interferon is one of the earlier therapies that we've had for this indication. Over the past 50 years, we have been using interferon with variable success. There has been a lot of progress since [it was first introduced to the landscape].

Initially, the biological version of the molecule was very similar to the natural interferon molecule; that resulted in significant anticancer activity but also significant adverse events (AEs). Over the years, we were able to fine-tune the treatment. We were also able to develop new molecules that continue to have the same activity with a much better side effect profile. Pegylated interferon is a lot more convenient, safer, and is better tolerated.

Could you elaborate on the different generations of the drug?  

The older versions of interferon were short-acting and required dosing on a daily basis or every other day; that resulted in significant AEs due to the fluctuation in interferon levels in the body. [Interferon] often had to be discontinued because of AEs, so patients were not able to stay on them for a long time. The more recent products that have been available for the last 20 years have been chemically modified to allow [the treatment] to function for a longer duration of time. Patients who had significant AEs [with older generations] were able to stay on the interferon for a longer period of time and had better long-term tolerance and results [with the recent products].

There are no FDA-approved products, so a lot of what we use is off-label. [Genentech’s]

peginterferon alfa-2a is the most commonly used version; it’s administered weekly with titration options in the dose and the schedule. Peginterferon alfa-2a is the agent we have the most experience with. There is also a newer, longer-acting version called ropeginterferon alfa-2b that is not yet commercially available in the United States. Most of the experience in the United States and Europe has been with peginterferon alfa-2a. Most of the published literature used that drug, although a lot of the upcoming studies are evaluating the use of the longer-acting ropeginterferon alfa-2b. 

What is the current role of interferon in the treatment of patients with MPNs?

Interferon provides a very unique therapeutic strategy for these patients. It's one of the safest drugs we can give them. It's a drug we use for younger patients, pregnant women, and those who want [children in the future]. We can also use it long-term without concerns of secondary toxicity, whereas the long-term use of other medications and chemotherapeutic agents are known to induce toxicities, including the possibility of a second cancer. The safety allows us to advocate for early interferon use in certain patient populations.

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