Prior studies have reported high response rates with recombinant interferon-a (rIFN-a) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-a,we investigated the outcomes of pegylated-rIFN-a2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PVwho were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 monthswere 69.2%(43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P 5 .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was 26% (range, 284%to 47%) in patients achieving a CR vs 14%(range, 218% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU.

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea / A. Yacoub, J. Mascarenhas, H. Kosiorek, J.T. Prchal, D. Berenzon, M.R. Baer, E. Ritchie, R.T. Silver, C. Kessler, E. Winton, M.C. Finazzi, A. Rambaldi, A.M. Vannucchi, D. Leibowitz, D. Rondelli, M.O. Arcasoy, R. Catchatourian, J. Vadakara, V. Rosti, E. Hexner, M. Kremyanskaya, L. Sandy, J. Tripodi, V. Najfeld, N. Farnoud, E. Papaemmanuil, M. Salama, R. Singer-Weinberg, R. Rampal, J.D. Goldberg, T. Barbui, R. Mesa, A.C. Dueck, R. Hoffman. - In: BLOOD. - ISSN 0006-4971. - 134:18(2019 Oct), pp. 1498-1509.

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea

M.C. Finazzi;A. Rambaldi;
2019

Abstract

Prior studies have reported high response rates with recombinant interferon-a (rIFN-a) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-a,we investigated the outcomes of pegylated-rIFN-a2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PVwho were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 monthswere 69.2%(43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P 5 .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was 26% (range, 284%to 47%) in patients achieving a CR vs 14%(range, 218% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU.
Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Drug Resistance, Neoplasm; Female; Humans; Hydroxyurea; Interferon-alpha; Male; Middle Aged; Polycythemia Vera; Polyethylene Glycols; Recombinant Proteins; Thrombocythemia, Essential; Treatment Outcome
Settore MED/15 - Malattie del Sangue
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/725015
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