From the Guidelines
Ruxolitinib (Jakafi) and interferon-alpha are the primary new medication options for essential polycythemia, with ruxolitinib being approved for patients who are resistant or intolerant to hydroxyurea, as evidenced by the 2018 European LeukemiaNet revised management recommendations 1.
New Medication Options
The treatment of essential polycythemia has evolved to include several newer medication options beyond traditional phlebotomy and hydroxyurea.
- Ruxolitinib (Jakafi), a JAK1/2 inhibitor, is now approved for polycythemia vera patients who are resistant or intolerant to hydroxyurea, with a typical starting dose of 10 mg twice daily, which may be adjusted based on response and tolerability 1.
- Interferon-alpha preparations, particularly pegylated forms like peginterferon alfa-2a (Pegasys), offer another important option, typically administered as subcutaneous injections at 45-180 mcg weekly, with potential for reduced frequency as the disease stabilizes.
Mechanism of Action and Benefits
- Ruxolitinib effectively reduces spleen size and controls symptoms like itching, night sweats, and bone pain by blocking the JAK-STAT pathway that drives the disease.
- Interferons work by suppressing abnormal bone marrow cell proliferation and can achieve molecular remission in some patients, making them especially valuable for younger patients and women of childbearing age since they don't carry the leukemogenic risk of hydroxyurea.
Side Effects and Monitoring
- Common side effects of ruxolitinib include anemia, thrombocytopenia, and infections, while interferons often cause flu-like symptoms, depression, and thyroid abnormalities, requiring careful monitoring during treatment.
Pregnancy Considerations
In the context of pregnancy, interferon-alpha is recommended for high-risk and select low-risk essential thrombocythemia (ET) and polycythemia vera (PV) patients with a history of recurrent fetal loss, prominent splenomegaly, or suboptimal hematocrit control with phlebotomy, as suggested by the 2021 American Journal of Hematology overview and practice recommendations 1.
From the Research
New Medication Options for Essential Polycythemia
- Ruxolitinib (Jakafi) is a Janus kinase (JAK) 1 and JAK2 inhibitor that has been shown to be effective in controlling hematocrit levels in patients with polycythemia vera (PV) without splenomegaly 2.
- Interferon-alpha (IFN-alpha) is another treatment option for PV and essential thrombocythemia (ET), and can be used as a first-line or second-line therapy 3, 4.
- Hydroxyurea is a commonly used cytoreductive therapy for high-risk ET and PV, but some patients may be intolerant or refractory to this treatment 3, 5, 6.
- Ruxolitinib has been shown to improve symptoms in patients with ET who are intolerant or refractory to hydroxyurea 6.
- The choice of treatment for PV and ET depends on the individual patient's risk category, with high-risk patients requiring more aggressive treatment to prevent thrombosis 3, 4, 5.
Treatment Algorithms
- A risk-adapted treatment algorithm for ET has been proposed, which takes into account the patient's age, thrombosis history, and JAK2/MPL mutations 5.
- The algorithm recommends hydroxyurea as the first-line cytoreductive treatment for high-risk ET, with ruxolitinib or IFN-alpha as second-line options 5, 6.
- For PV, the treatment algorithm recommends phlebotomy to keep hematocrit levels below 45%, as well as aspirin therapy to prevent thrombosis 3, 4.
Clinical Outcomes
- Studies have shown that ruxolitinib can improve hematocrit control and reduce the need for phlebotomies in patients with PV 2.
- Ruxolitinib has also been shown to improve symptoms and reduce the risk of thrombosis in patients with ET 6.
- Hydroxyurea has been shown to be effective in reducing leukocyte and platelet counts in patients with ET, but some patients may experience intolerance or resistance to this treatment 6.