From the Guidelines
The recommended treatment regimen for preventing thrombotic events in high-risk essential thrombocythemia (ET) patients is a combination of pegylated interferon alfa-2a (Pegasys) plus low-dose aspirin, as demonstrated by recent studies 1. This combination therapy has shown superior efficacy in reducing thrombotic events compared to traditional regimens such as hydroxyurea plus aspirin. The typical dosing regimen involves subcutaneous pegylated interferon alfa-2a starting at 45 mcg weekly, which can be titrated up to 180 mcg weekly as tolerated, along with aspirin 81-100 mg daily.
Key considerations for this treatment regimen include:
- Monitoring patients regularly for side effects of interferon therapy, including flu-like symptoms, fatigue, and potential thyroid dysfunction 1
- Dose adjustments may be necessary based on platelet count response and tolerability
- The mechanism behind this regimen's effectiveness involves interferon's ability to selectively target the malignant clone of cells in ET while preserving normal hematopoiesis, along with aspirin's antiplatelet effects that reduce the risk of arterial thrombosis
It's worth noting that the European LeukemiaNet guidelines favor hydroxyurea as first-line therapy for ET patients in need of cytoreduction, but recent phase 2 trials have reported that pegylated interferon alpha-2a can induce durable hematological and molecular responses in patients with ET 1. Additionally, a phase 3 non-inferiority trial documented that anagrelide proved noninferior when compared to hydroxyurea in the prevention of thrombotic complications, but the evidence was judged moderate 1.
In terms of specific patient populations, low-dose acetyl salicylic acid has been shown to be effective in preventing vascular events in ET patients, particularly in those with JAK2V617F-mutated patients, and may be associated with a reduced incidence of venous thrombosis with no effect on the risk of bleeding 1. However, in CALR-mutated patients, antiplatelet therapy did not affect the risk of thrombosis but was associated with higher incidence of bleeding 1.
Overall, the combination of pegylated interferon alfa-2a and low-dose aspirin is a recommended treatment regimen for preventing thrombotic events in high-risk ET patients, with careful consideration of individual patient factors and potential side effects.
From the Research
Treatment Regimen for High-Risk Essential Thrombocythemia (ET)
The SURPASS-ET trial is not directly mentioned in the provided evidence. However, based on the available studies, the following information can be gathered:
- Hydroxyurea is effective in preventing thrombosis in high-risk patients with essential thrombocythemia 2.
- Anagrelide is also used to reduce elevated platelet counts in patients with essential thrombocythemia, but its use is associated with increased rates of arterial thrombosis and serious hemorrhage compared to hydroxyurea 3, 4.
- A combination of low-dose hydroxyurea and anagrelide may be a feasible approach with lower toxicity compared to monotherapy 5.
- Aspirin is suggested for most patients with essential thrombocythemia to lower thrombosis risk, and cytoreduction with hydroxyurea can significantly lower the risk of arterial or venous thrombotic events in high-risk patients 6.
Key Findings
- Hydroxyurea plus low-dose aspirin is superior to anagrelide plus low-dose aspirin for patients with essential thrombocythemia at high risk for vascular events 4.
- The use of aspirin and cytoreductive therapy, such as hydroxyurea, should be based on individual risk factors for thrombosis 6.
- A combination of low-dose hydroxyurea and anagrelide may be considered as an alternative strategy for patients who experience side effects from prior monotherapy 5.
Treatment Options
- Hydroxyurea plus low-dose aspirin
- Anagrelide plus low-dose aspirin (although associated with increased rates of arterial thrombosis and serious hemorrhage)
- Combination of low-dose hydroxyurea and anagrelide (may be considered as an alternative strategy)