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Clinical Trial
. 2009 Nov 10;27(32):5418-24.
doi: 10.1200/JCO.2009.23.6075. Epub 2009 Oct 13.

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

Alfonso Quintás-Cardama  1 , Hagop Kantarjian, Taghi Manshouri, Rajyalakshmi Luthra, Zeev Estrov, Sherry Pierce, Mary Ann Richie, Gautam Borthakur, Marina Konopleva, Jorge Cortes, Srdan Verstovsek
Affiliations
Clinical Trial

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

Alfonso Quintás-Cardama et al. J Clin Oncol. .

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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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Response to pegylated interferon alfa-2a therapy. (A) Hematologic response in patients with essential thrombocythemia (ET) or polycythemia vera (PV). (B) Cumulative incidence of complete hematologic response (CHR) and partial hematologic response (PHR). (C) Cumulative incidence of complete molecular response (CMR), partial molecular response (PMR), minor molecular response (mMR), and overall molecular response. (D) Dynamics of molecular response for the six patients (two with ET and four with PV) who achieved a CMR.
Fig 2.
Fig 2.
Dynamics of JAK2V617F mutant allele burden in patients with essential thrombocythemia (ET) or polycythemia vera (PV) who achieved molecular response (n = 25) during the first 24 months of pegylated interferon alfa-2a therapy. The JAK2V617F mutation was quantitated using a pyrosequencing assay. Black horizontal lines denote median values; black bars represent minimum and maximum values; and blue rectangular areas represent values included between the 25% and the 75% percentiles.
See this image and copyright information in PMC

References

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