{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:39:03Z","timestamp":1792600743062,"version":"4.5.0"},"reference-count":58,"publisher":"Harborside Press, LLC","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>Interferons are cytokines with immunomodulatory properties that have been used in the treatment of myeloproliferative neoplasms (MPNs) for decades. However, their widespread use has been hampered by their adverse effect profile and difficulty with administration. Recently there has been a resurgence of interest in the use of interferons in MPNs given the development of pegylated formulations with improved tolerability. Currently, treatments for polycythemia vera (PV) and essential thrombocythemia (ET) are targeted toward decreasing the risk of thrombotic complications, because there are no approved therapies that are known to modify disease. However, recent data on interferons in MPNs have suggested the potential for disease-modifying activity, including the achievement of molecular remission and sustained clinical response. This development has led to the question of whether interferons should move forward as the preferred frontline cytoreductive agent for ET and PV, and challenges the criteria currently used to initiate therapy. We review randomized controlled trial data evaluating interferon\u2019s efficacy and tolerability in patients with ET and PV. We then consider the data in the context of interferon\u2019s known advantages and disadvantages to address whether interferons should be the first choice for cytoreductive treatment in patients with ET and PV.<\/jats:p>","DOI":"10.6004\/jnccn.2022.7026","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T19:38:00Z","timestamp":1662665880000},"page":"1063-1068","source":"Crossref","is-referenced-by-count":8,"title":["Interferons as the First Choice of Cytoreduction in Essential Thrombocythemia and Polycythemia Vera"],"prefix":"10.6004","volume":"20","author":[{"given":"Joan","family":"How","sequence":"first","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Hobbs","sequence":"additional","affiliation":[{"name":"2Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"ref171","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1182\/blood-2013-01-478891","article-title":"Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project","volume":"121","author":"Barosi","year":"2013","journal-title":"Blood"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1038\/leu.2008.280","article-title":"Interferon-alpha therapy in bcr-abl-negative myeloproliferative neoplasms","volume":"22","author":"Kiladjian","year":"2008","journal-title":"Leukemia"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1016\/S2352-3026(17)30030-3","article-title":"Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial","volume":"4","author":"Masarova","year":"2017","journal-title":"Lancet Haematol"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1182\/blood-2020-141223","article-title":"Interferon-alpha (IFN) therapy discontinuation is feasible in myeloproliferative neoplasm (MPN) patients with complete hematological remission [abstract]","volume":"136","author":"Daltro De Oliveira","year":"2020","journal-title":"Blood"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"e196","DOI":"10.1016\/S2352-3026(19)30236-4","article-title":"Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study","volume":"7","author":"Gisslinger","year":"2020","journal-title":"Lancet Haematol"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1038\/s41375-020-01020-4","article-title":"Interferon alpha therapy in essential thrombocythemia and polycythemia vera\u2014a systematic review and meta-analysis","volume":"35","author":"Bewersdorf","year":"2021","journal-title":"Leukemia"},{"key":"ref591","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2021-147869","article-title":"A JAK2V617F variant allele frequency greater than 50% identifies patients with polycythemia vera at high risk for venous thrombosis [abstract]","volume":"138","author":"Loscocco","year":"2021","journal-title":"Blood"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1016\/S2352-3026(17)30030-3","article-title":"Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial","volume":"4","author":"Masarova","year":"2017","journal-title":"Lancet Haematol"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/S2352-3026(21)00343-4","article-title":"Symptom burden and quality of life in patients with high-risk essential thrombocythaemia and polycythaemia vera receiving hydroxyurea or pegylated interferon alfa-2a: a post-hoc analysis of the MPN-RC 111 and 112 trials","volume":"9","author":"Mazza","year":"2022","journal-title":"Lancet Haematol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1056\/NEJM199504273321704","article-title":"Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis","volume":"332","author":"Cortelazzo","year":"1995","journal-title":"N Engl J Med"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1038\/s41375-021-01183-8","article-title":"Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival","volume":"35","author":"Abu-Zeinah","year":"2021","journal-title":"Leukemia"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e369","DOI":"10.1038\/bcj.2015.94","article-title":"Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia","volume":"5","author":"Barbui","year":"2015","journal-title":"Blood Cancer J"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nature07815","article-title":"IFN\u03b1 activates dormant haematopoietic stem cells in vivo","volume":"458","author":"Essers","year":"2009","journal-title":"Nature"},{"key":"ref551","doi-asserted-by":"crossref","first-page":"e485","DOI":"10.1097\/HS9.0000000000000485","article-title":"Ropeginterferon alfa-2b: efficacy and safety in different age groups","volume":"4","author":"Gisslinger","year":"2020","journal-title":"HemaSphere"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.1182\/blood-2012-05-432989","article-title":"Depletion of Jak2V617F myeloproliferative neoplasm-propagating stem cells by interferon-\u03b1 in a murine model of polycythemia vera","volume":"121","author":"Mullally","year":"2013","journal-title":"Blood"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.1182\/blood-2012-05-432989","article-title":"Depletion of Jak2V617F myeloproliferative neoplasm-propagating stem cells by interferon-\u03b1 in a murine model of polycythemia vera","volume":"121","author":"Mullally","year":"2013","journal-title":"Blood"},{"key":"ref451","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1182\/blood.V91.2.616","article-title":"Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion","volume":"91","author":"Sterkers","year":"1998","journal-title":"Blood"},{"key":"ref491","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2018-99-111255","article-title":"Long-term efficacy and safety of recombinant interferon alpha-2 vs. hydroxyurea in polycythemia vera: preliminary results from the three-year analysis of the DALIAH trial\u2014a randomized controlled phase III clinical trial [abstract]","volume":"132","author":"Knudsen","year":"2018","journal-title":"Blood"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1200\/JCO.2011.34.7542","article-title":"Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms","volume":"29","author":"Bj\u00f6rkholm","year":"2011","journal-title":"J Clin Oncol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1182\/blood-2010-08-258772","article-title":"The renaissance of interferon therapy for the treatment of myeloid malignancies","volume":"117","author":"Kiladjian","year":"2011","journal-title":"Blood"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s41375-018-0077-1","article-title":"Philadelphia chromosome- negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet","volume":"32","author":"Barbui","year":"2018","journal-title":"Leukemia"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa1208500","article-title":"Cardiovascular events and intensity of treatment in polycythemia vera","volume":"368","author":"Marchioli","year":"2013","journal-title":"N Engl J Med"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1056\/NEJM199504273321704","article-title":"Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis","volume":"332","author":"Cortelazzo","year":"1995","journal-title":"N Engl J Med"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1200\/JCO.2011.34.7542","article-title":"Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms","volume":"29","author":"Bj\u00f6rkholm","year":"2011","journal-title":"J Clin Oncol"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1182\/blood.V91.2.616","article-title":"Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion","volume":"91","author":"Sterkers","year":"1998","journal-title":"Blood"},{"key":"ref581","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1182\/blood.2021010986","article-title":"Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFN\u03b1 in myeloproliferative neoplasms","volume":"138","author":"Mosca","year":"2021","journal-title":"Blood"},{"key":"ref571","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1038\/s41375-021-01183-8","article-title":"Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival","volume":"35","author":"Abu-Zeinah","year":"2021","journal-title":"Leukemia"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1182\/blood.2021012743","article-title":"A randomized, phase 3, trial of interferon-\u03b1 versus hydroxyurea in polycythemia vera and essential thrombocythemia","volume":"139","author":"Mascarenhas","year":"2022","journal-title":"Blood"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1182\/blood.2021012743","article-title":"A randomized, phase 3, trial of interferon-\u03b1 versus hydroxyurea in polycythemia vera and essential thrombocythemia","volume":"139","author":"Mascarenhas","year":"2022","journal-title":"Blood"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1182\/bloodadvances.2021004856","article-title":"Genomic profiling of a randomized trial of interferon-\u03b1 versus hydroxyurea in MPN reveals mutation-specific responses","volume":"6","author":"Knudsen","year":"2022","journal-title":"Blood Adv"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1182\/blood.2021010986","article-title":"Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFN\u03b1 in myeloproliferative neoplasms","volume":"138","author":"Mosca","year":"2021","journal-title":"Blood"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1182\/blood-2012-07-444067","article-title":"Development and validation of an International Prognostic Score of thrombosis in World Health Organization\u2014essential thrombocythemia (IPSET-thrombosis)","volume":"120","author":"Barbui","year":"2012","journal-title":"Blood"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/(SICI)1096-8652(199605)52:1<42::AID-AJH7>3.0.CO;2-6","article-title":"Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis","volume":"52","author":"Nand","year":"1996","journal-title":"Am J Hematol"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1182\/blood-2010-08-258772","article-title":"The renaissance of interferon therapy for the treatment of myeloid malignancies","volume":"117","author":"Kiladjian","year":"2011","journal-title":"Blood"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"e369","DOI":"10.1038\/bcj.2015.94","article-title":"Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia","volume":"5","author":"Barbui","year":"2015","journal-title":"Blood Cancer J"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s41375-018-0077-1","article-title":"Philadelphia chromosome- negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet","volume":"32","author":"Barbui","year":"2018","journal-title":"Leukemia"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1182\/bloodadvances.2021004856","article-title":"Genomic profiling of a randomized trial of interferon-\u03b1 versus hydroxyurea in MPN reveals mutation-specific responses","volume":"6","author":"Knudsen","year":"2022","journal-title":"Blood Adv"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1200\/JCO.2014.57.6652","article-title":"Risk and cause of death in patients diagnosed with myeloproliferative neoplasms in Sweden between 1973 and 2005: a population-based study","volume":"33","author":"Hultcrantz","year":"2015","journal-title":"J Clin Oncol"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1200\/JCO.2014.57.6652","article-title":"Risk and cause of death in patients diagnosed with myeloproliferative neoplasms in Sweden between 1973 and 2005: a population-based study","volume":"33","author":"Hultcrantz","year":"2015","journal-title":"J Clin Oncol"},{"key":"ref511","doi-asserted-by":"crossref","first-page":"e196","DOI":"10.1016\/S2352-3026(19)30236-4","article-title":"Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study","volume":"7","author":"Gisslinger","year":"2020","journal-title":"Lancet Haematol"},{"key":"ref561","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1182\/blood-2020-141223","article-title":"Interferon-alpha (IFN) therapy discontinuation is feasible in myeloproliferative neoplasm (MPN) patients with complete hematological remission [abstract]","volume":"136","author":"Daltro De Oliveira","year":"2020","journal-title":"Blood"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1038\/leu.2008.280","article-title":"Interferon-alpha therapy in bcr-abl-negative myeloproliferative neoplasms","volume":"22","author":"Kiladjian","year":"2008","journal-title":"Leukemia"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1182\/blood-2012-07-444067","article-title":"Development and validation of an International Prognostic Score of thrombosis in World Health Organization\u2014essential thrombocythemia (IPSET-thrombosis)","volume":"120","author":"Barbui","year":"2012","journal-title":"Blood"},{"key":"ref291","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2021-147869","article-title":"A JAK2V617F variant allele frequency greater than 50% identifies patients with polycythemia vera at high risk for venous thrombosis [abstract]","volume":"138","author":"Loscocco","year":"2021","journal-title":"Blood"},{"key":"ref521","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1016\/S2352-3026(20)30373-2","article-title":"Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial","volume":"8","author":"Barbui","year":"2021","journal-title":"Lancet Haematol"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/leu.2017.230","article-title":"Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status","volume":"32","author":"Kubesova","year":"2018","journal-title":"Leukemia"},{"key":"ref191","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2018-99-111255","article-title":"Long-term efficacy and safety of recombinant interferon alpha-2 vs. hydroxyurea in polycythemia vera: preliminary results from the three-year analysis of the DALIAH trial\u2014a randomized controlled phase III clinical trial [abstract]","volume":"132","author":"Knudsen","year":"2018","journal-title":"Blood"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.beha.2014.07.003","article-title":"Leukemic transformation in myeloproliferative neoplasms: therapy-related or unrelated?","volume":"27","author":"Bj\u00f6rkholm","year":"2014","journal-title":"Best Pract Res Clin Haematol"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"e485","DOI":"10.1097\/HS9.0000000000000485","article-title":"Ropeginterferon alfa-2b: efficacy and safety in different age groups","volume":"4","author":"Gisslinger","year":"2020","journal-title":"HemaSphere"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/leu.2017.230","article-title":"Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status","volume":"32","author":"Kubesova","year":"2018","journal-title":"Leukemia"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/S2352-3026(21)00343-4","article-title":"Symptom burden and quality of life in patients with high-risk essential thrombocythaemia and polycythaemia vera receiving hydroxyurea or pegylated interferon alfa-2a: a post-hoc analysis of the MPN-RC 111 and 112 trials","volume":"9","author":"Mazza","year":"2022","journal-title":"Lancet Haematol"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nature07815","article-title":"IFN\u03b1 activates dormant haematopoietic stem cells in vivo","volume":"458","author":"Essers","year":"2009","journal-title":"Nature"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/(SICI)1096-8652(199605)52:1<42::AID-AJH7>3.0.CO;2-6","article-title":"Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis","volume":"52","author":"Nand","year":"1996","journal-title":"Am J Hematol"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.beha.2014.07.003","article-title":"Leukemic transformation in myeloproliferative neoplasms: therapy-related or unrelated?","volume":"27","author":"Bj\u00f6rkholm","year":"2014","journal-title":"Best Pract Res Clin Haematol"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa1208500","article-title":"Cardiovascular events and intensity of treatment in polycythemia vera","volume":"368","author":"Marchioli","year":"2013","journal-title":"N Engl J Med"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1182\/blood-2013-01-478891","article-title":"Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project","volume":"121","author":"Barosi","year":"2013","journal-title":"Blood"},{"key":"ref531","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1038\/s41375-020-01020-4","article-title":"Interferon alpha therapy in essential thrombocythemia and polycythemia vera\u2014a systematic review and meta-analysis","volume":"35","author":"Bewersdorf","year":"2021","journal-title":"Leukemia"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1016\/S2352-3026(20)30373-2","article-title":"Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial","volume":"8","author":"Barbui","year":"2021","journal-title":"Lancet Haematol"}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/20\/9\/article-p1063.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/20\/9\/article-p1063.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T19:22:26Z","timestamp":1662751346000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/20\/9\/article-p1063.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":58,"journal-issue":{"issue":"9"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2022.7026","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9]]}}}