{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:02:34Z","timestamp":1791442954858,"version":"4.3.3"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Myelofibrosis is characterized by perturbation of the JAK\/STAT pathway and upregulation of anti\u2010apoptotic factors leading to myeloproliferation, bone marrow fibrosis (BMF), extramedullary hematopoiesis, splenomegaly, and cytopenias. Navitoclax, a potent oral B\u2010cell lymphoma (BCL)\u2010X\n                      <jats:sub>L<\/jats:sub>\n                      \/BCL\u20102 inhibitor, promotes apoptosis of malignant myelofibrosis cells. Herein, we present results of Cohort 3 of the Phase 2 REFINE study (NCT03222609), which evaluated efficacy and safety of navitoclax plus ruxolitinib in JAKi\u2010na\u00efve patients with myelofibrosis. JAKi\u2010na\u00efve patients with primary or secondary myelofibrosis (\u2265 18 years with splenomegaly, DIPSS intermediate\u20102 and high\u2010risk myelofibrosis, and ECOG 0\u20132) and platelet count &gt; 100 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L were enrolled and treated with navitoclax 100 mg once daily (QD) or 200 mg QD according to platelet count (\u2264 150 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L or &gt; 150 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L, respectively). Ruxolitinib was given twice daily (dose per label). Primary endpoint: spleen volume reduction of \u2265\u00a035% (SVR\n                      <jats:sub>35<\/jats:sub>\n                      ) at week 24. Secondary endpoints: \u2265\u00a050% reduction in total symptom score (TSS\n                      <jats:sub>50<\/jats:sub>\n                      ) at week 24, change in grade of BMF, anemia response, and safety. Thirty\u2010two patients received \u2265\u00a01 dose of navitoclax plus ruxolitinib. Median (range) duration of follow\u2010up was 44\u00a0months (5\u201358). 63% (20\/32) of patients achieved SVR\n                      <jats:sub>35<\/jats:sub>\n                      at week 24; median (range) time to first SVR\n                      <jats:sub>35<\/jats:sub>\n                      was 12\u00a0weeks (11\u250048). Of 24 evaluable patients, 21% achieved \u2265\u00a050% reduction in driver gene variant allele frequency (VAF). Of 27 evaluable patients, 11 (41%) achieved TSS\n                      <jats:sub>50<\/jats:sub>\n                      at week 24; median (range) time to first TSS\n                      <jats:sub>50<\/jats:sub>\n                      of 3\u00a0weeks (0\u250016). BMF improved from baseline by\u00a0\u2265\u00a01 grade in 13\/27 patients (48%) at any time on study. Anemia response rates were 38% (5\/13) for transfusion\u2010independent and 100% (2\/2) for transfusion\u2010dependent patients. No bleeding events or deaths were attributed to navitoclax. These findings suggest navitoclax plus ruxolitinib has a tolerable safety profile and provides clinically meaningful improvements for JAKi\u2010na\u00efve patients with myelofibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>NCT03222609.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hon.70180","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:11:36Z","timestamp":1773814296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor\u2010Na\u00efve Patients With Myelofibrosis From the Multicenter, Open\u2010Label, Phase 2 Study (REFINE)"],"prefix":"10.1002","volume":"44","author":[{"given":"Francesco","family":"Passamonti","sequence":"first","affiliation":[{"name":"Dipartimento di Oncologia ed Onco\u2010Ematologia Universit\u00e0 degli Studi di Milano Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1673-1708","authenticated-orcid":false,"given":"James M.","family":"Foran","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Tandra","sequence":"additional","affiliation":[{"name":"Indiana Blood and Marrow Transplant  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Section of Hematology Department of Radiological and Hematological Sciences Catholic University  Rome Italy"},{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Hematology Hospital Universitari Vall d'Hebron Experimental Hematology Vall d'Hebron Institute of Oncology (VHIO) Vall d'Hebron Hospital Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Mattour","sequence":"additional","affiliation":[{"name":"Henry Ford Hospital  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0773-0204","authenticated-orcid":false,"given":"Mary Frances","family":"McMullin","sequence":"additional","affiliation":[{"name":"Centre for Medical Education Queen\u02bcs University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3644-7093","authenticated-orcid":false,"given":"Andrew C.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Australian Centre for Blood Diseases Monash University and the Alfred Hospital  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Rodriguez\u2010Mac\u00edas","sequence":"additional","affiliation":[{"name":"Department of Hematology Hospital General Universitario Gregorio Mara\u00f1\u00f3n Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan A.","family":"Sibai","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology Princess Margaret Cancer Centre University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshanth R.","family":"Polepally","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  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