{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:39:39Z","timestamp":1790746779123,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Incyte Corporation, Wilmington, DE, USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ruxolitinib (JAK1\/JAK2 inhibitor) is indicated for adults with intermediate or high-risk myelofibrosis; however, a subset of patients may exhibit a suboptimal response due to persistent PI3K\/AKT activation. The phase 3, randomized, double-blind, placebo-controlled LIMBER-304 study (NCT04551053) investigated the efficacy and safety of add-on parsaclisib (highly selective PI3K\u03b4 inhibitor) in patients with myelofibrosis and suboptimal or declining response to stable ruxolitinib monotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Adults with primary or secondary myelofibrosis who received ruxolitinib with palpable spleen and Myelofibrosis Symptom Assessment Form (MFSAF) total symptom score (TSS) \u226510 were eligible. Primary end point was proportion of patients achieving \u226525% spleen volume reduction (SVR; baseline to week 24); key secondary end point was proportion of patients with \u226550% MFSAF-TSS reduction (baseline to week 24).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 90 patients received parsaclisib\/ruxolitinib; 87 received placebo\/ruxolitinib. At week 24, 16.7% of patients receiving parsaclisib\/ruxolitinib achieved \u226525% SVR vs 9.7% for placebo\/ruxolitinib; this difference was not statistically significant. By week 24, \u226550% reduction in MFSAF-TSS was observed in 17.1% of patients receiving parsaclisib\/ruxolitinib vs 14.1% for placebo\/ruxolitinib. Higher rates of infections (including cytomegalovirus) and gastrointestinal disorders were observed with parsaclisib\/ruxolitinib. Grade \u22653 treatment-emergent adverse events occurred in 60.0% of patients receiving parsaclisib\/ruxolitinib vs 42.5% with placebo\/ruxolitinib. The study was terminated early based on efficacy findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Study results suggested adding parsaclisib to stable-dose ruxolitinib was unlikely to offer clinically meaningful benefits. Further research is needed on the potential of JAK and PI3K inhibitor-based combination therapy for patients with myelofibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag201","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:39:37Z","timestamp":1779190777000},"source":"Crossref","is-referenced-by-count":2,"title":["Add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: a randomized phase 3 study"],"prefix":"10.1093","volume":"31","author":[{"given":"Jean-Jacques","family":"Kiladjian","sequence":"first","affiliation":[{"name":"Saint-Louis Hospital, Paris Cit\u00e9 University, INSERM , Paris 75010,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Borate","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. 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Jebsen Center for Myeloid Blood Cancer, University of Bergen , Bergen 5009,","place":["Norway"]},{"name":"Department of Medicine, Haukeland University Hospital , Bergen, 5009,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Rein","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine , Durham, NC 27710,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulraheem","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center, Westwood Campus , Westwood, KS 66205,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Incyte Corporation , Wilmington, DE 19803,","place":["United 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