{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:26:44Z","timestamp":1793467604854,"version":"4.5.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"GSK"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and\/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1\/JAK2\/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (<jats:italic>n<\/jats:italic>\u00a0=\u00a0156). Patient subgroups (<jats:italic>n<\/jats:italic>\u00a0=\u00a0105 each) were defined by either baseline (1) hemoglobin (Hb) of\u00a0&lt;\u00a0100\u00a0g\/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of\u00a0&lt;\u00a080\u00a0g\/L for the previous 12\u00a0weeks); outcomes have been summarized descriptively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT\/ruxolitinib: baseline Hb of\u00a0&lt;\u00a0100\u00a0g\/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT\/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT\/ruxolitinib were lower.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In patients with moderate-to-severe anemia and\/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia\u00a0supportive therapies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial Registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov: NCT02101268.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12325-024-02928-4","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T15:33:53Z","timestamp":1720712033000},"page":"3722-3735","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Momelotinib versus Continued Ruxolitinib or Best Available Therapy in JAK Inhibitor-Experienced Patients with Myelofibrosis and Anemia: Subgroup Analysis of SIMPLIFY-2"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-920X","authenticated-orcid":false,"given":"Claire N.","family":"Harrison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro M.","family":"Vannucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Recher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Passamonti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron T.","family":"Gerds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Hernandez-Boluda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulraheem","family":"Yacoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shireen","family":"Sirhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Strouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Platzbecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"issue":"1","key":"2928_CR1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000001","volume":"1","author":"L Naymagon","year":"2017","unstructured":"Naymagon L, Mascarenhas J. 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Alessandro M. Vannucchi reports honoraria from Incyte, Novartis, BMS, GSK, AbbVie, Roche, and AOP. Christian Recher reports honoraria from and an advisory role with AbbVie, Astellas, Amgen, BMS, Jazz Pharmaceuticals, Novartis, and Servier and research funding from AbbVie, Astellas, Amgen, BMS, Jazz Pharmaceuticals, and Servier. Francesco Passamonti reports honoraria from AbbVie, AOP Orphan, and Bristol Myers Squibb\/Celgene and consultancy with AbbVie, AOP Orphan, Celgene, Bristol Myers Squibb, Janssen, Kartos, Karyopharm, Kyowa Kirin, MEI, Novartis, Roche, Sierra Oncology, and Sumitomo. Aaron T. Gerds reports consultancy with AbbVie, Bristol Myers Squibb, Celgene, Constellation Pharmaceuticals, GSK, Kartos, Novartis, PharmaEssentia, and Sierra Oncology; consultancy with and research funding from CTI BioPharma, Imago BioSciences\/Merck, and Constellation Pharmaceuticals\/MorphoSys; research funding from Accurate Pharmaceuticals, Constellation Pharmaceuticals, CTI BioPharma, Imago BioSciences, Incyte Corporation, and Kartos Pharmaceuticals; and an advisory role with AbbVie, Bristol Myers Squibb, CTI BioPharma, GSK, Imago, Kartos, MorphoSys, PharmaEssentia, and Rain Oncology. Juan Carlos Hernandez-Boluda reports an advisory role with Incyte, Pfizer, Novartis, and BMS. Abdulraheem Yacoub reports consultancy with Incyte, CTI Pharma, PharmaEssentia, Pfizer, Novartis, and Acceleron Pharma. Shireen Sirhan reports honoraria from Constellation and consultancy with and honoraria from GSK, Novartis, and Constellation. Catherine Ellis, Bharat Patel, and Bryan Strouse are employees of GSK. Uwe Platzbecker reports consultancy with AbbVie, Curis, and Geron and an advisory role with MDS Foundation. All authors acknowledge editorial support in the preparation of this manuscript, funded by GSK.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The study protocol was approved by the institutional review board or independent ethics committee at each study site (Supplementary Material), and all participants provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"\u00a0Ethical Approval"}}]}}