A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia

John Mascarenhas*, Heidi E. Kosiorek, Josef T. Prchal, Alessandro Rambaldi, Dmitriy Berenzon, Abdulraheem Yacoub, Claire N. Harrison, Mary Frances McMullin, Alessandro M. Vannucchi, Joanne Ewing, Casey L. O'Connell, Jean Jacques Kiladjian, Adam J. Mead, Elliott F. Winton, David S. Leibowitz, Valerio De Stefano, Murat O. Arcasoy, Craig M. Kessler, Rosalind Catchatourian, Damiano RondelliRichard T. Silver, Andrea Bacigalupo, Arnon Nagler, Marina Kremyanskaya, Max F. Levine, Juan E. Arango Ossa, Erin McGovern, Lonette Sandy, Mohamad E. Salama, Vesna Najfeld, Joseph Tripodi, Noushin Farnoud, Alexander V. Penson, Rona Singer Weinberg, Leah Price, Judith D. Goldberg, Tiziano Barbui, Roberto Marchioli, Gianni Tognoni, Raajit K. Rampal, Ruben A. Mesa, Amylou C. Dueck, Ronald Hoffman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.

Original languageEnglish
Pages (from-to)2931-2941
Number of pages11
Issue number19
StatePublished - 12 May 2022
Externally publishedYes


FundersFunder number
Roche Genentech1K08CA188529-01
National Institutes of Health5P01CA108671-09
National Cancer InstituteP30CA008748


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