Efficacy and safety of pegylated interferon alpha-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV): results of a phase 2 study after a 7-year median follow-up

BACKGROUND: The durability of responses and long-term safety of pegylated interferon alpha-2a (PEG-IFN-a-2a) in patients with polycythemia vera and essential thrombocythemia have not been reported. Here, we present long-term efficacy and safety data from a single-center, prospective, phase 2 study, after 7 years of follow-up. METHODS: Patients older than 18 years who were diagnosed with essential thrombocythemia or polycythemia vera per 2001 World Health Organization criteria were eligble to enroll. Responses were assessed every 3–6 months: Data were analyzed using descriptive statistics. The rate of leukemia transformation was compared with age- and gender-matched patients who were not treated with PEG-IFN-α-2a. FINDINGS: PEG-IFN-α-2a induced hematologic (80%) and molecular responses (63%) in 83 patients with essential thrombocythemia (n=40) and polycythemia vera (n=43), with median durations of 66 and 53 months, respectively. Thirty-nine percent of hematologic responders and 71% of molecular responders (JAK2V617F+) have maintained some response during follow-up: 48% maintained their best molecular response, including 9 of 10 patients with a complete molecular response. The incidence of major venous-thrombotic events during the study was 1.22/person-year. Overall, 22% of patients discontinued therapy due to treatment-related toxicity. While toxicity rates decreased over time, 5 patients experienced treatment-limiting G3/4 toxicities after 60 months on therapy. Rates of transformation to MF/AML were similar between patients treated with PEG-IFN-a-2a and those from a historical control series. INTERPRETATION: PEG-IFN-α-2a can induce durable hematologic and molecular remissions in patients with essential thrombocythemia and polycythemia vera. We suggest a starting dose of 45 mcg/week, and its combination with other drugs should be explored further in clinical trials.