From the Guidelines
Interferon therapy in polycythemia vera (PV) does improve myelofibrosis-free and overall survival, as evidenced by its ability to induce hematologic response rates of up to 80%. The use of interferon alfa-2 (IFN-2) or pegylated IFN has been shown to be effective in the therapy of PV, with pegylated IFN demonstrating clinical efficacy in phase II trials, including normalization of myeloproliferation, lack of vascular events while on therapy, and a decrease in the JAK2V617F allele burden 1.
Key Points
- Interferon works by directly inhibiting the proliferation of JAK2-mutated hematopoietic progenitor cells, reducing the malignant clone burden, and normalizing blood counts.
- It also has anti-inflammatory and immunomodulatory effects that help prevent disease progression to myelofibrosis.
- Clinical studies have demonstrated that interferon therapy can induce molecular remissions with reductions in JAK2 V617F allele burden, decrease the risk of thrombotic events, and significantly delay or prevent progression to myelofibrosis compared to conventional cytoreductive therapies like hydroxyurea.
- The survival benefit is particularly notable in younger patients who can tolerate longer treatment courses, though side effects including flu-like symptoms, fatigue, depression, and thyroid dysfunction require monitoring.
Treatment Considerations
- Either hydroxyurea or IFN- is first-line cytoreductive therapy at any age, with hydroxyurea used with caution in young patients (ie, age < 40 years) 1.
- Pegylated interferon alpha is the preferred formulation due to its better tolerability and once-weekly dosing schedule.
- Treatment typically begins at a lower dose and is gradually increased based on response and tolerability, with treatment duration often extending for years as PV is a chronic condition.
From the Research
Interferon in Polycythemia Vera
- Interferon-alpha (rIFNα) is a disease-modifying treatment for polycythemia vera (PV) that has been shown to improve myelofibrosis-free and overall survival 2.
- A large single-center retrospective study of 470 PV patients found that rIFNα was associated with improved 20-year myelofibrosis-free survival (MFS) and overall survival (OS) compared to hydroxyurea (HU) and phlebotomy-only (PHL-O) 2.
- In low-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 84%, 65%, and 55%, respectively, and 20-year OS was 100%, 85%, and 80%, respectively 2.
- In high-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 89%, 41%, and 36%, respectively, and 20-year OS was 66%, 40%, and 14%, respectively 2.
- Multivariable analysis found that longer time on rIFNα was associated with a lower risk of myelofibrosis and lower mortality 2.
Mechanism of Action
- Interferon-alpha (IFN) inhibits the growth of the abnormal clone in patients with myeloproliferative disorders, leading to a reduction of the clinical and laboratory signs of the pathologic myeloproliferation 3.
- The selective suppression of the malignant clone by IFN was demonstrated by the induction of cytogenetic remissions in sporadic cases with a chromosomal marker and by the observation of unmaintained remissions that lasted up to 4.8 years 3.
Current Treatment Guidelines
- Current goal of therapy is to prevent thrombosis, and periodic phlebotomy with a hematocrit target of <45%, combined with once- or twice-daily aspirin (81 mg) therapy, is the backbone of treatment in all patients, regardless of risk category 4.
- Cytoreductive therapy is reserved for high-risk disease, with first-line drugs of choice being hydroxyurea and pegylated interferon-α, and second-line busulfan and ruxolitinib 4.
- Interferons remain a preferred first-line cytoreductive agent, with the JAK1 and JAK2 inhibitor, ruxolitinib, currently approved for the treatment of patients who are resistant to, or intolerant of, hydroxyurea 5.