Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera

Alfonso Quintás-Cardama, Hagop Kantarjian, Taghi Manshouri, Rajyalakshmi Luthra, Zeev Estrov, Sherry Pierce, Mary Ann Richie, Gautam Borthakur, Marina Konopleva, Jorge Cortes, Srdan Verstovsek

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260 Scopus citations

Abstract

Purpose: We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-α-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-α-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-α-2a at 450 μg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 μg 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 JAK2V617F 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 JAK2V617F) 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-α-2a at 90 μg weekly was excellent. Conclusion: PEG-IFN-α-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-α-2a to induce complete molecular responses suggests selective targeting of the malignant clone.

Original languageEnglish (US)
Pages (from-to)5418-5424
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number32
DOIs
StatePublished - Nov 10 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Quintás-Cardama, A., Kantarjian, H., Manshouri, T., Luthra, R., Estrov, Z., Pierce, S., Richie, M. A., Borthakur, G., Konopleva, M., Cortes, J., & Verstovsek, S. (2009). Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. Journal of Clinical Oncology, 27(32), 5418-5424. https://doi.org/10.1200/JCO.2009.23.6075