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

• Type of Material: Article
• Authors: John Mascarenhas, Icahn School of Medicine at Mount Sinai; Heidi E Kosiorek, Mayo Clinic, Scottsdale; Josef T Prchal, University of Utah; Alessandro Rambaldi, ASST Papa Giovanni XXIII; Dmitriy Berenzon, Wake Forest Baptist Health, Comprehensive Cancer Center; Abdulraheeem Yacoub, Kansas University Cancer Center; Claire N Harrison, Guy’s Hospital, London; Mary Frances McMullin, Queens University Belfast; Alessandro M Vannucchi, University of Florence; Joanne Ewing, Heart of England NHS Foundation Trust, UHB; Casey L O'Connell, University of Southern California; Jean-Jacques Kiladjian, Université de Paris; Adam J Mead, Oxford University Hospitals NHS Foundation Trust; Elliott Winton, Emory University; David S Leibowitz, Palo Alto Medical Foundation Sutter Health; Valerio De Stefano, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS; Murat O Arcasoy, Duke University; Craig M Kessler, Georgetown University; Rosalind Catchatourian, John H. Stroger Jr Hospital of Cook County; Damiano Rondelli, University of Illinois at Chicago; Richard T Silver, New York Presbyterian Weill Cornell Med Ctr; Andrea Bacigalupo, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS); Arnon Nagler, Chaim Sheba Medical Center; Marina Kremyanskaya, Icahn School of Medicine at Mount Sinai; Max F Levine, Memorial Sloan-Kettering Cancer Center; Juan Arango E Ossa, Memorial Sloan-Kettering Cancer Center; Erin McGovern, Memorial Sloan-Kettering Cancer Center; Lonette Sandy, Icahn School of Medicine at Mount Sina; Mohamad E Salama, Mayo Clinic, Rochester; Vesna Najfeld, Icahn School of Medicine at Mount Sinai; Joseph Tripodi, Icahn School of Medicine at Mount Sina; Noushin Farnoud, Memorial Sloan-Kettering Cancer Center; Alexander Penson, Memorial Sloan-Kettering Cancer Center; Rona Singer Weinberg, New York Blood Center; Leah Price, New York University; Judith D Goldberg, New York University; Tiziano Barbui, Papa Giovanni XXIII Hosp; Roberto Marchioli, Renal and Metabolic Medical and Scientific Services, IQVIA; Gianni Tognoni, Ospedale Maggiore Policlinico; Raajit K Rampal, Memorial Sloan-Kettering Cancer Center; Ruben A Mesa, UT Health San Antonio Cancer Center; Amylou C Dueck, Mayo Clinic, Scottsdale; Ronald Hoffman, Icahn School of Medicine at Mount Sinai
• Language: English
• Date: 2022-05-12
• Publisher: AMER SOC HEMATOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by The American Society of Hematology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/blood.2021012743
• Title of Journal or Parent Work: BLOOD
• Volume: 139
• Issue: 19
• Start Page: 2931
• End Page: 2941
• Grant/Funding Information: This work was supported by a grant from the National Cancer Institute, National Institutes of Health (MPN Research Consortium, 5P01CA108671-09), a Cancer Center Support Grant/Core grant to Memorial Sloan-Kettering Cancer Center (P30 CA008748), and generous independent, unrestricted support from Roche Genentech. R.K.R. is supported by the National Cancer Institute, National Institutes of Health (1K08CA188529-01).
• Keywords: Life Sciences & Biomedicine; NEOPLASMS; GROWTH; Science & Technology; Hematology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

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.