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  • Title: Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera.
    Author: Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S.
    Journal: J Clin Oncol; 2009 Nov 10; 27(32):5418-24. PubMed ID: 19826111.
    Abstract:
    PURPOSE: We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-alpha-2a) in patients with essential thrombocythemia (ET) and polycythemia vera (PV). PATIENTS AND METHODS: Seventy-nine patients (40 with PV and 39 with ET) have been treated. Median time from diagnosis to PEG-IFN-alpha-2a was 54 months in patients with PV and 33 months in patients with ET. Eighty-one percent of patients had received prior therapy. The first three patients received PEG-IFN-alpha-2a at 450 microg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 microg weekly. Seventy-seven patients are evaluable and have been observed for a median of 21 months. RESULTS: The overall hematologic response rate was 80% in PV and 81% in ET (complete in 70% and 76% of patients, respectively). The JAK2(V617F) mutation was detected in 18 patients with ET and 38 patients with PV; sequential measurements by a pyrosequencing assay were available in 16 patients with ET and 35 patients with PV. The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2(V617F)) in 6% and 14%, respectively. The JAK2(V617F) mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability of PEG-IFN-alpha-2a at 90 microg weekly was excellent. CONCLUSION: PEG-IFN-alpha-2a resulted in remarkable clinical activity, high rates of molecular response, and acceptable toxicity in patients with advanced ET or PV. The ability of PEG-IFN-alpha-2a to induce complete molecular responses suggests selective targeting of the malignant clone.
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