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At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non\u2010JAKi agents are being actively explored (in combination with ruxolitinib in first\u2010line or salvage settings and\/or as monotherapy in JAKi\u2010pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B\u2010cell lymphoma 2\/B\u2010cell lymphoma 2\u2010xL inhibitor), parsaclisib (a phosphoinositide 3\u2010kinase inhibitor), navtemadlin (formerly KRT\u2010232; a murine double\u2010minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non\u2010JAKi treatments to modify the natural history of MF.<\/jats:p>","DOI":"10.1002\/cncr.34222","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T11:50:09Z","timestamp":1649245809000},"page":"2717-2727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes"],"prefix":"10.1002","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8400-0483","authenticated-orcid":false,"given":"John O.","family":"Mascarenhas","sequence":"first","affiliation":[{"name":"Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srdan","family":"Verstovsek","sequence":"additional","affiliation":[{"name":"Leukemia 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