Hydroxyurea vs. Pegylated Interferon in Essential Thrombocythemia and Polycythemia Vera

The most effective first-line treatment for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is unknown. Hydroxyurea (HU) is the most commonly used treatment for high-risk patients. However, over the last decade, reports of hematological and molecular responses in patients treated with pegylated interferon-α (peg-IFN) have renewed enthusiasm for this agent.

In an international, randomized, controlled trial, investigators compared the safety and efficacy of peg-IFN and HU in 168 high-risk patients with ET or PV. High risk was defined as presence of at least one of the following: age >60; thrombosis history; bleeding (ET only); platelet count >1000 x 10⁹/L in PV and >1500 x 10⁹/L in ET; vasomotor symptoms; splenomegaly; diabetes; or hypertension. The primary endpoint was complete response (CR), defined as normalization of blood counts, spleen size, and disease-related symptoms.

Among the findings:

• CR at 12 months was similar in the HU and peg-IFN groups (37% and 35%; P=0.80).
• Median spleen size reduction was similar in the HU and peg-IFN groups (−5% and −6%).
• Cumulative incidence of thrombosis was 2% in each group.
• Histopathological bone marrow response was significantly more common in the HU group (23% vs. 5%).
• Molecular responses were observed in both the HU and peg-IFN groups (−5.3% and −10.7%).
• Adverse events were more common in the peg-IFN group than the HU group, including depression (15% vs. 3%) and grade 3 or higher events (46% vs. 28%).