{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:46:00Z","timestamp":1789011960147,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1\/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-na\u00efve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR\u2009=\u20091.02 [0.73, 1.43];\u00a0LFS HR\u2009=\u20091.08 [0.78, 1.50]). Two-year OS and LFS were 81.6% and 80.7% with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib. In ruxolitinib-exposed patients in SIMPLIFY-2, two-year OS and LFS were 65.8% and 64.2% with momelotinib and 61.2% and 59.7% with best available therapy then momelotinib (OS HR\u2009=\u20090.98 [0.59, 1.62]; LFS HR\u2009=\u20090.97 [0.59, 1.60]). Baseline transfusion independence (TI) was associated with improved survival in both studies (SIMPLIFY-1 HR\u2009=\u20090.474,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0001; SIMPLIFY-2 HR\u2009=\u20090.226,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0005). Week 24 TI response in JAKi-na\u00efve, momelotinib-randomized patients was associated with improved OS in univariate (HR\u2009=\u20090.323;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and multivariate (HR\u2009=\u20090.311;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) analyses. These findings underscore the importance of achieving or maintaining TI in myelofibrosis, supporting the clinical relevance of momelotinib\u2019s pro-erythropoietic mechanism of action, and potentially informing treatment decision-making.\n                  <\/jats:p>","DOI":"10.1038\/s41375-022-01637-7","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T10:04:25Z","timestamp":1658484265000},"page":"2261-2268","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis"],"prefix":"10.1038","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5880-7972","authenticated-orcid":false,"given":"Ruben","family":"Mesa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-5400","authenticated-orcid":false,"given":"Stephen T.","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-1309","authenticated-orcid":false,"given":"Aaron T.","family":"Gerds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-8607","authenticated-orcid":false,"given":"Vikas","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Catalano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Cervantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Devos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Hus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8121-438X","authenticated-orcid":false,"given":"Jean-Jacques","family":"Kiladjian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Lech-Maranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-091X","authenticated-orcid":false,"given":"Donal","family":"McLornan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro M.","family":"Vannucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-3239","authenticated-orcid":false,"given":"Uwe","family":"Platzbecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Strouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-2526","authenticated-orcid":false,"given":"Barbara","family":"Klencke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-8569","authenticated-orcid":false,"given":"Srdan","family":"Verstovsek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"1637_CR1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/ajh.26050","volume":"96","author":"A Tefferi","year":"2021","unstructured":"Tefferi A. 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Claire Harrison has received grants or contracts from Celgene\/Bristol-Myers Squibb, Constellation, and Novartis; consulting fees from Keros, Galecto, AOP Orphan Pharmaceuticals, and Roche; payments or honoraria from Novartis, Celgene, CTI Biopharma, AbbVie, Janssen, and Constellation; support to attending meetings from Novartis; and has participated on Data Safety Monitoring or Advisory Boards for Galecto, CTI Biopharma, Roche, Geron, Promedior, AbbVie, AOP Orphan Pharmaceuticals, and Sierra Oncology, in addition to leadership or fiduciary roles in EHA and MPN Voice. Stephen T. Oh has received consulting fees from CTI Biopharma, Celgene\/Bristol-Myers Squibb, Incyte, Blueprint Medicines, AbbVie, Sierra Oncology, Disc Medicine, Constellation, and PharmaEssentia. Aaron T. Gerds has participated in Data Safety Monitoring or Advisory Boards at Sierra Oncology, CTI Biopharma, Incyte, AbbVie, Celgene\/Bristol-Myers Squibb, Morphosys, Novartis, and PharmEssentia. Vikas Gupta has received consulting fees from Novartis, Celgene\/Bristol-Myers Squibb, Sierra Oncology, AbbVie, Constellation, and Pfizer; payment or honoraria from Novartis, Celgene\/Bristol-Myers Squibb, and Constellation; and has participated on Data Safety Monitoring or Advisory Boards for Celgene\/Bristol-Myers Squibb, Roche, AbbVie, and Pfizer. John Catalano states no conflicts of interest. Francisco Cervantes has received consulting feeds from Bristol-Myers Squibb; payment or honoraria from Pfizer; and support for attending meetings from Bristol-Myers Squibb. Timothy Devos has received consulting fees for Novartis, Celgene\/Bristol-Myers Squibb, Morphosys, and AbbVie. Marek Hus states no conflicts of interest. Jean-Jacques Kiladjian has received consulting fees from Novartis, Celgene\/Bristol-Myers Squibb, and AOP Orphan Pharmaceuticals; payment or honoraria from Novartis; and has participated in Data Safety Monitoring or Advisory Boards for Incyte. Ewa Lech-Maranda has participated in Data Safety Monitoring or Advisory Boards for AbbVie, Roche, Gilead, and Novartis. Donal McLornan has received research funding from Novartis; royalties from a book on myelofibrosis; payment or honoraria from Nocartis, Jazz, and AbbVie, and has participated on a Data Safety Monitoring Board for the UK ALLRIC trial. Alessandro M. Vannucchi has received payment or honoraria from Novartis, AbbVie, Celgene\/Bristol-Myers Squibb, and AOP Orphan Pharmaceuticals; participated in Data Safety Monitoring and Advisory Boards with Incyte, Novartis, Celgene\/Bristol-Myers Squibb, AbbVie, GlaxoSmithKline, and AOP Orphan Pharmaceuticals. Uwe Platzbecker has received consulting fees from AbbVie, Novartis, Celgene\/Bristol-Myers Squibb, Janssen, Curis, and Geron; payment or honoraria from Novartis, Takeda, Celgene\/Bristol-Myers Squibb, Janssen, and Jazz Pharmaceuticals; and has participated on Data Safety Monitoring or Advisory Boards for Novartis, AbbVie, and Celgene\/Bristol-Myers Squibb. Mei Huang, Bryan Strouse, and Barbara Klencke are employees of and claim stock options from Sierra Oncology. Srdan Verstovsek has received consulting fees from Sierra Oncology.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"COMPETING INTERESTS"}}]}}