{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:41:37Z","timestamp":1792683697755,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/\/\/doi.org\/10.13039\/100008792","name":"Novartis | Novartis Pharma","doi-asserted-by":"publisher","award":["CINC424BDE09T"],"award-info":[{"award-number":["CINC424BDE09T"]}],"id":[{"id":"10.13039\/\/\/doi.org\/10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/\/\/doi.org\/10.13039\/100008792","name":"Novartis | Novartis Pharma","doi-asserted-by":"publisher","award":["CINC424BDE09T"],"award-info":[{"award-number":["CINC424BDE09T"]}],"id":[{"id":"10.13039\/\/\/doi.org\/10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ruxolitinib (RUX) is approved as second-line treatment for HU-intolerant\/-resistant patients with polycythemia vera (PV). Here, we assessed RUX vs. best available therapy (BAT) as first-line treatment in PV in the randomized multicenter RuxoBEAT clinical trial (NCT02577926). Crossover from BAT to RUX was possible after 6 months. Baseline characteristics in the RUX (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200944) and BAT (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200934) arms were comparable. The primary endpoint, the clinico-hematologic complete response (CR) rate at month 6, was not met (2.3% vs. 2.9%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.000). Analyses of secondary and exploratory endpoints showed that RUX was significantly more effective than BAT in improving hematocrit, splenomegaly, and patient-reported pruritus and fatigue, but less effective in reducing platelet counts. Compared to baseline, JAK2V617F variant allele frequency decreased significantly in both RUX and BAT groups at 6 months. The time on treatment (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and duration of treatment (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.022) were significantly superior for RUX vs. BAT during the 24-month study period. There were no new safety signals. These findings demonstrate that RUX did not lead to higher CR rates than BAT and suggest that RUX may induce clinically meaningful additional disease improvements in first-line therapy of PV patients.\n                  <\/jats:p>","DOI":"10.1038\/s41408-026-01644-2","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:47:18Z","timestamp":1792680438000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Firstline treatment with ruxolitinib versus best available therapy in patients with polycythemia vera: results from the randomized RuxoBEAT trial"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1011-8171","authenticated-orcid":false,"given":"Steffen","family":"Koschmieder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Isfort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9489-7282","authenticated-orcid":false,"given":"Lino L.","family":"Teichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Schafhausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian H.","family":"Heidel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Crodel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hochhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8718-7004","authenticated-orcid":false,"given":"Martin","family":"Griesshammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-7299","authenticated-orcid":false,"given":"Katja","family":"Sockel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp J.","family":"Jost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Walther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2261-9862","authenticated-orcid":false,"given":"Konstanze","family":"D\u00f6hner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim R.","family":"G\u00f6thert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Radsak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinela","family":"Augustin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristoteles","family":"Giagounidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schaich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Klausmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas","family":"von Bubnoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Stegelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Kortmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Zentis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hagemeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hellmich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim H.","family":"Br\u00fcmmendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the German Study Group for Myeloproliferative Neoplasms (GSG-MPN)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"1644_CR1","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1038\/s41375-018-0077-1","volume":"32","author":"T Barbui","year":"2018","unstructured":"Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32:1057\u201369.","journal-title":"Leukemia"},{"key":"1644_CR2","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1182\/blood-2011-01-328955","volume":"118","author":"R Scherber","year":"2011","unstructured":"Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. 2011;118:401\u20138.","journal-title":"Blood"},{"key":"1644_CR3","doi-asserted-by":"publisher","first-page":"e301","DOI":"10.1016\/S2352-3026(22)00046-1","volume":"9","author":"M Marchetti","year":"2022","unstructured":"Marchetti M, Vannucchi AM, Griesshammer M, Harrison C, Koschmieder S, Gisslinger H, et al. Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations. Lancet Haematol. 2022;9:e301\u2013e11.","journal-title":"Lancet Haematol"},{"key":"1644_CR4","doi-asserted-by":"crossref","unstructured":"Koschmieder S, Schulte C, von der Heyde E, Busque L, Boyer-Perrard F, Devos T, et al. Clinical outcomes of high-risk patients with polycythemia vera after suboptimal response to first-line therapy who switched to ruxolitinib versus nonswitchers: results from the PV-Switch study. Ther Adv Hematol. 2025;16:20406207251342199.","DOI":"10.1177\/20406207251342199"},{"key":"1644_CR5","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1056\/NEJMoa1409002","volume":"372","author":"AM Vannucchi","year":"2015","unstructured":"Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372:426\u201335.","journal-title":"N Engl J Med"},{"key":"1644_CR6","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/S1470-2045(16)30558-7","volume":"18","author":"F Passamonti","year":"2017","unstructured":"Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, et al. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017;18:88\u201399.","journal-title":"Lancet Oncol"},{"key":"1644_CR7","doi-asserted-by":"publisher","first-page":"3534","DOI":"10.1200\/JCO.22.01935","volume":"41","author":"CN Harrison","year":"2023","unstructured":"Harrison CN, Nangalia J, Boucher R, Jackson A, Yap C, O\u2019Sullivan J, et al. Ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial. J Clin Oncol. 2023;41:3534\u201344.","journal-title":"J Clin Oncol"},{"key":"1644_CR8","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s00277-022-05080-7","volume":"102","author":"S Koschmieder","year":"2023","unstructured":"Koschmieder S, Isfort S, Wolf D, Heidel FH, Hochhaus A, Schafhausen P, et al. Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group. Ann Hematol. 2023;102:349\u201358.","journal-title":"Ann Hematol"},{"key":"1644_CR9","doi-asserted-by":"publisher","first-page":"4829","DOI":"10.1182\/blood-2008-09-176818","volume":"113","author":"G Barosi","year":"2009","unstructured":"Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. 2009;113:4829\u201333.","journal-title":"Blood"},{"key":"1644_CR10","doi-asserted-by":"publisher","first-page":"4778","DOI":"10.1182\/blood-2013-01-478891","volume":"121","author":"G Barosi","year":"2013","unstructured":"Barosi G, Mesa R, Finazzi G, Harrison C, Kiladjian JJ, Lengfelder E, et al. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood. 2013;121:4778\u201381.","journal-title":"Blood"},{"key":"1644_CR11","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.1007\/s00277-022-05000-9","volume":"101","author":"M Kalmer","year":"2022","unstructured":"Kalmer M, Pannen K, Lemanzyk R, Wirths C, Baumeister J, Maurer A, et al. Clonogenic assays improve determination of variant allele frequency of driver mutations in myeloproliferative neoplasms. Ann Hematol. 2022;101:2655\u201363.","journal-title":"Ann Hematol"},{"key":"1644_CR12","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1182\/blood-2011-10-387787","volume":"119","author":"A Alvarez-Larran","year":"2012","unstructured":"Alvarez-Larran A, Pereira A, Cervantes F, Arellano-Rodrigo E, Hernandez-Boluda JC, Ferrer-Marin F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood. 2012;119:1363\u20139.","journal-title":"Blood"},{"key":"1644_CR13","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1182\/blood-2023-173225","volume":"142","author":"S Koschmieder","year":"2023","unstructured":"Koschmieder S, Isfort S, Teichmann LL, Schafhausen P, Heidel F, Hochhaus A, et al. Firstline treatment with ruxolitinib versus best available therapy in patients with polycythemia vera: pre-specified interim analysis of the randomized phase 2b ruxobeat clinical trial of the German Study Group for Myeloproliferative Neoplasms (GSG-MPN). Blood. 2023;142:619.","journal-title":"Blood"},{"key":"1644_CR14","unstructured":"Team RC. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https:\/\/www.r-project.org\/ 2016."},{"key":"1644_CR15","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1007\/s00277-017-3082-y","volume":"96","author":"CN Harrison","year":"2017","unstructured":"Harrison CN, Koschmieder S, Foltz L, Guglielmelli P, Flindt T, Koehler M, et al. The impact of myeloproliferative neoplasms (MPNs) on patient quality of life and productivity: results from the international MPN Landmark survey. Ann Hematol. 2017;96:1653\u201365.","journal-title":"Ann Hematol"}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41408-026-01644-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-026-01644-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-026-01644-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:57:12Z","timestamp":1792681032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41408-026-01644-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":15,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1644"],"URL":"https:\/\/doi.org\/10.1038\/s41408-026-01644-2","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"17 July 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S. Koschmieder reports research funding from Novartis, Bristol-Myers Squibb, AOP Pharma, Janssen, Geron; advisory board honoraria from Pfizer, Incyte, Ariad, Novartis, AOP Pharma, BMS, Celgene, Geron, Janssen, CTI, Roche, Baxalta, Sanofi, Sierra Oncology, GSK, Abbvie, PharmaEssentia, Protagonist, Takeda, MSD; patent for BET inhibitor. at RWTH Aachen University; honoraria from Novartis, BMS, Celgene, Geron, Janssen, Pfizer, Incyte, Ariad, Shire, Roche, AOP Pharma, GSK, Abbvie, MPN Hub, iOMEDICO, MSD, and Astra Zeneca, Protagonist, Takeda; and other financial support (e.g., travel support) from Alexion, Novartis, BMS, Incyte, Ariad, AOP Pharma, Baxalta, CTI, Pfizer, Sanofi, Celgene, Shire, Janssen, Geron, Abbvie, Karthos, Sierra Oncology, Imago Bioscience, GSK, Abbvie, iOMEDICO, Protagonist, Takeda, MSD. S. Isfort reports advisory board honoraria from Pfizer, Incyte, GSK and Novartis, honoraria from Novartis, BMS, Pfizer, Incyte, AOP Orphan; and other financial support (e.g., travel support) from Alexion, Novartis, Pfizer, Mundipharma, Roche, Hexal, AOP Orphan. L. L. Teichmann received honoraria from AOP, BMS, GSK, Novartis; served as an advisor for Astellas, Blueprint, BMS, GSK, Jazz Pharmaceuticals, Novartis, Pfizer, Sobi; received conference fees from Abbvie, AOP, BeiGene, Gilead, Jazz Pharmaceuticals. P. Schafhausen reports consulting\/advisory role\/honoraria\/travel and accommodation support from Alexion, AOP Orphan, Blueprint Medicines, BMS\/Celgene, Merck Serono, MSD, Novartis, Pfizer, Roche and Sobi. F. H. Heidel reports consultancy and honoraria from Novartis, AOP Orphan, CTI Biopharma, BMS, AbbVie, Pfizer, Janssen, Sumitomo, Geron, GSK, MSD, Prelude, Silence, Takeda, and Kartos and received research funding from Novartis, CTI Biopharma and BMS. C. Crodel reports consulting\/advisory role\/honoraria\/travel and accommodation support from Novartis, BMS, GSK, MSD, Astra Zeneca and BeOne. A. Hochhaus received research support by Novartis, BMS, Pfizer, Incyte. M. Griesshammer reports consultancy for and honoraria from AOP Orphan, Novartis, BMS, AbbVie, Pfizer, Roche, Janssen, Gilead, AstraZeneca, Sierra, Lilly, GSK. K. Sockel received research funding from Active Biotech, honoraria from Novartis, BMS\/Celgene, Gilead, SOBI and served as advisor for Novartis. P. J. Jost has had a consulting or advisory role, received honoraria, research funding, and\/or travel\/accommodation expenses from: Astra Zeneca, Ipsen, Gilead, Amgen, Eli Lilly, Merck, MSD, Bayer, Boehringer, Novartis, Pfizer, Servier, Roche, BMS and Celgene, Pierre Fabre, Janssen \/ Johnson&Johnson, MSD and is shareholder, employee and board member of Cycuria Therapeutics and shareholders of Vessel FlexCo. K. D\u00f6hner reports speaker bureau and consultancy for BMS, Celgene, CTI, Novartis, and Roche. J. R. G\u00f6thert received payment or honoraria from Proteros Biostructures, pharma&, BMS, Blueprint medicines, Incyte, Ariad, Pfizer, Novartis AOP Pharma, GlaxoSmithKline and MSD; received travel support from BeiGene, BMS, Incyte, Novartis,AOP Pharma and Takeda; participated on advisory boards for Abbvie, Pfizer, Incyte, Ariad, Novartis, AOP Pharma, BMS, CTI BioPharma, Imago Bioscience, GlaxoSmithKline, MSD and Takeda. M. Radsak received consulting fees and honoraria from Pfizer, Novartis, SOBI, MSD, Lilly, GSK, Alexion, Merck, BeOne, BMS, Johnson & Johnson, AOP, AstraZeneca, AbbVie, Cogent, RYVU, Sanofi; travel support from SOBI, AOP, AbbVie, Johnson & Johnson, BeOne, and research funding from the Foundation \u201cLichterzellen\u201d, EKFS, and DFG. M. Augustin reports research funding from Janssen-Cilag, AstraZeneca, Bayer, BMS, EXELIXIS, IPSEN, Lilly, Merck, MSD, Novartis, Pfizer, PharmaMar, Roche, IMMATICS, honoraria for advisory role from Janssen-Cilag, AstraZeneca, Bayer, Bristol-Myers Squibb, IPSEN, Blueprint Medicines, PharmaMar, EISAI, travel support from Janssen-Cilag, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Novartis, Pfizer, PharmaMar, Lilly, Merck. H. Becker reports honoraria from and consultancy for Abbvie, Astellas, BMS\/Celgene, GSK, Lilly, MSD, Novartis, Pierre Fabre Pharma, Servier, Takeda. M. Schaich reports honoraria from and consultancy for AbbVie, Celgene, Janssen, Novartis, Pfizer and Sobi. N. von Bubnoff received honoraria from Novartis, Blueprint, GSK, BMS and MSD, and received travel support from Janssen. F. Stegelmann reports honoraria from and consultancy for Abbvie, AOP Pharma, BMS\/Celgene, GSK, Incyte, MorphoSys, Novartis and Pfizer. The Institute of Medical Statistics and Computational Biology (J. Frank, A. Hagemeier, and M. Hellmich) received funding from the sponsor of the study (RWTH Aachen University) for statistical planning and analysis. T. H. Br\u00fcmmendorf served as consultant\/speaker for Gilead, Janssen, Merck, Novartis, Pfizer, and received research support from Novartis and Pfizer. The other coauthors reported no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"189"}}