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Richard T. Silver MD Myeloproliferative Neoplasms Center

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Interferons

Interferons are signaling proteins made by your body when it is fighting infections (viruses, bacteria, parasites) or tumor cells. There are many different classes of interferon produced by your body. Several interferon types have been developed as drugs to treat a variety of disorders ranging from virus infections such as hepatitis to neurologic disorders like multiple sclerosis. Although they are not approved by the FDA for this indication, alpha interferons have been repeatedly shown to be effective treatment for myeloproliferative neoplasms (MPNs).

Interferons are different from traditional chemotherapy drugs in that they are cytokines (signaling proteins) that work within the body’s natural defense system by affecting cell function and growth. Prior to the introduction of tyrosine kinase inhibitors (TKIs) such as imatinib, higher dose interferon was arguably the best therapy for chronic myeloid leukemia (CML) in patients who could not receive an allogenic bone marrow transplant. Now, interferons are rarely if ever used in CML. However, interferons are frequently used to treat patients with polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). The interferon doses useful in these Philadephia chromosome negative (Ph-neg MPNs; PV, ET, MF) are much lower dose than those previously used in CML or those used to treat hepatitis. The lower doses required for Ph-neg MPNs and newer interferon formulations make these drugs much easier for patients to take than they were in the past.

Interferons are thought to act on normal blood cells and MPN cells differently but it is not known exactly how interferon works in these diseases. This is an area we at the Silver MPN Center are actively investigating with collaborators around the world in order to learn how to best use interferon for the treatment of MPNs.

Interferons remain important drugs for the treatment of PV, ET and MF because they are the only agents known to do more than control the blood counts and reduce clotting risk. Interferons have been repeatedly shown to actually reduce the number of MPN cells in the bone marrow and blood. Interferon has even been shown to reverse bone marrow fibrosis in some patients with MF. Dr. Silver, for whom the Richard T. Silver MPN Center was named, was an early pioneer in the use of interferon in MPNs.

There are a few different types of interferon medications used for MPNs.

Both interferon-α2a (trade name, Roferon-A), interferon-α2b (trade name, Intron A) have been shown to be effective but it is not known if one is better than the other. More important are differences in how the interferon is formulated for clinical use. When interferon is attached to a biologically inert chemical called polyethylene glycol, or PEG, it lasts in the blood stream longer. This has the benefit of requiring less frequent injections. Peginterferons (peginterferon-α2a marketed as Pegasys; and peginterferon-α2b marketed as Pegintron) also seem to have fewer side effects, presumably because the blood levels change less quickly.

Interferon is given as an injection under the skin. Whereas non-modified interferons are normally injected three times per week, peginterferons can be administered weekly. New interferon formulations are in development that only need to be injected every two to four weeks. Interferon needs to be kept cold and this can require some planning when patients travel.

    Side Effects

    Common side effects:

    Many of these side effects go away over time but some can worsen. It is important that you report to your medical team any side effect you think you may be experiencing.

    • Injection site reactions (pain, swelling, redness may occur at the injection site)
    • Flu-like symptoms
    • Headache
    • Tiredness
    • Diarrhea, upset stomach
    • Loss of appetite
    • Muscle/back pain
    • Dizziness
    • Dry mouth
    • Taste changes
    • Nausea/vomiting
    • Mental/mood changes

    Potentially Serious Side Effects:
    Interferon acts as a natural part of the body’s immune system. For this reason, treatment with interferons can cause a variety of uncommon side effects that relate to the breadth of its normal biological functions. Some of these side effects can be severe and it is important that you discuss report to your medical team any side effects you may be experiencing. Before making a decision to begin interferon therapy, it’s important to review with your physician the relative risks and benefits of interferon treatment. Your past history of inflammatory/autoimmune disorders, depression and neuropathy are particularly important.

    • Although uncommon, autoimmune disorders can be triggered or made worse by interferon therapy. Sometimes this does not go away even if the interferon is stopped. Join swelling, aches and pains and changes in mood (depression or anger) may be caused by interferon and should be reported to your medical team right away.

    Additional Information: https://www.medicinenet.com/interferon/article.htm

    Richard T. Silver MD Myeloproliferative Neoplasms Center 525 East 70th St., Starr Pavillion, 3rd Floor New York, NY 10021 SilverMPNCenter@med.cornell.edu