{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T23:51:13Z","timestamp":1768434673555,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["374817"],"award-info":[{"award-number":["374817"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Preclinical observations that killing of chronic lymphocytic leukemia (CLL) cells was dexamethasone (DEX) were enhanced by concomitant inhibition of Bruton\u2019s tyrosine kinase and janus kinases (JAKs) motivated a phase II trial to determine if clinical responses to ibrutinib could be deepened by DEX and the JAK inhibitor ruxolitinib. Patients on ibrutinib at 420\u00a0mg daily for 2\u00a0months or with abnormal serum \u03b22M levels after 6\u00a0months or with persistent lymphadenopathy or splenomegaly after 12\u00a0months were randomized to receive DEX 40\u00a0mg on days 1\u20134 of a 4\u2010week cycle for six cycles alone (three patients) or with ruxolitinib 15\u00a0mg BID on days 1\u201321 of each cycle (five patients). Ruxolitinib dosing was based on a previous phase I trial. Steroid withdrawal symptoms and significantly decreased serum IgG levels occurred in all patients regardless of their exposure to ruxolitinib. A fatal invasive fungal infection was seen in a patient taking DEX without ruxolitinib. Complete responses anticipated with addition of ruxolitinib were not seen. Gene expression studies suggested ruxolitinib had turned off interferon signaling in CLL cells and turned on genes associated with the activation of NF\u03baB by TNF\u2010\u03b1. Ruxolitinib increased blood levels of TNF\u2010\u03b1 by cycle 3 and decreased the inhibitory cytokine IL\u201010. These results suggest ruxolitinib releases activating signals for CLL cells that persist in patients on ibrutinib. This inhibitory JAK signaling may contribute to the therapeutic activity of ibrutinib. Thus JAK inhibitors provide no added value with ibrutinib for disease control and should be used with caution in CLL patients. Combining glucocorticoids with ibrutinib may increase the risk of serious infects.<\/jats:p>","DOI":"10.1002\/cam4.4378","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T07:52:18Z","timestamp":1637221938000},"page":"8789-8798","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Janus kinases restrain chronic lymphocytic leukemia cells in patients on ibrutinib: Results of a phase II trial"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0783-7554","authenticated-orcid":false,"given":"David E.","family":"Spaner","sequence":"first","affiliation":[{"name":"Biology Platform Sunnybrook Research Institute Toronto Ontario Canada"},{"name":"Department of Medical Biophysics University of Toronto Toronto Ontario Canada"},{"name":"Sunnybrook Odette Cancer Center Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto Toronto Ontario 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