{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:41:19Z","timestamp":1782963679129,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006694","name":"Associazione Italiana Contro le Leucemie - Linfomi e Mieloma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The authors performed a subanalysis of an observational, retrospective study (RUX\u2010MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A total of 219 patients (31.2%) discontinued ruxolitinib for \u226514 days and survived for \u226530 days. In 60 patients (27.4%), ruxolitinib was rechallenged for \u226514 days (RUX\u2010again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX\u2010stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack\/loss of spleen response was lower in RUX\u2010again patients (<jats:italic>P<\/jats:italic> = .004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (<jats:italic>P<\/jats:italic> &lt; .001) and a high Total Symptom Score (TSS; <jats:italic>P<\/jats:italic> &lt; .001). During the rechallenge, 44.6% and 48.3% of the patients had spleen and symptom improvements, respectively, with a significant increase in the number of patients with a TSS reduction (<jats:italic>P<\/jats:italic> = .01). Although the use of a ruxolitinib dose &gt; 10 mg twice daily predicted better spleen (<jats:italic>P<\/jats:italic> = .05) and symptom improvements (<jats:italic>P<\/jats:italic> = .02), the reasons for\/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX\u2010again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX\u2010again patients (<jats:italic>P<\/jats:italic> = .004).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33541","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T17:34:36Z","timestamp":1617298476000},"page":"2657-2665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8367-5668","authenticated-orcid":false,"given":"Francesca","family":"Palandri","sequence":"first","affiliation":[{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli,\u201d IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9449-2621","authenticated-orcid":false,"given":"Mario","family":"Tiribelli","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplantation Azienda Sanitaria Universitaria Integrata di Udine Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-6162","authenticated-orcid":false,"given":"Massimo","family":"Breccia","sequence":"additional","affiliation":[{"name":"Division of Cellular Biotechnologies and Hematology University Sapienza Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-2896","authenticated-orcid":false,"given":"Daniela","family":"Bartoletti","sequence":"additional","affiliation":[{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli,\u201d IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna Bologna Italy"},{"name":"Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Universit\u00e0 di Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena M.","family":"Elli","sequence":"additional","affiliation":[{"name":"Hematology Division and Bone Marrow Unit San Gerardo Hospital, Azienda Socio Sanitaria Territoriale Monza Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3200-9654","authenticated-orcid":false,"given":"Giulia","family":"Benevolo","sequence":"additional","affiliation":[{"name":"Division of Hematology Citt\u00e0 della Salute e della Scienza Hospital Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Martino","sequence":"additional","affiliation":[{"name":"Division of Hematology Azienda Ospedaliera \u201cBianchi Melacrino Morelli\u201d Reggio Calabria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cavazzini","sequence":"additional","affiliation":[{"name":"Division of Hematology University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Tieghi","sequence":"additional","affiliation":[{"name":"Department of Hematology Azienda Unit\u00e0 Sanitaria Locale\u2010IRCCS di Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-0812","authenticated-orcid":false,"given":"Alessandra","family":"Iurlo","sequence":"additional","affiliation":[{"name":"Hematology Division Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-6491","authenticated-orcid":false,"given":"Elisabetta","family":"Abruzzese","sequence":"additional","affiliation":[{"name":"Division of Hematology Ospedale S. 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