{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:21:36Z","timestamp":1793740896276,"version":"4.6.1"},"reference-count":27,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Signaling through JAK1 and\/or JAK2 is common among tumor and nontumor cells within peripheral T-cell lymphoma (PTCL). No oral therapies are approved for PTCL, and better treatments for relapsed\/refractory disease are urgently needed. We conducted a phase 2 study of the JAK1\/2 inhibitor ruxolitinib for patients with relapsed\/refractory PTCL (n = 45) or mycosis fungoides (MF) (n = 7). Patients enrolled onto 1 of 3 biomarker-defined cohorts: (1) activating JAK and\/or STAT mutations, (2) \u226530% pSTAT3 expression among tumor cells by immunohistochemistry, or (3) neither or insufficient tissue to assess. Patients received ruxolitinib 20 mg PO twice daily until progression and were assessed for response after cycles 2 and 5 and every 3 cycles thereafter. The primary endpoint was clinical benefit rate (CBR), defined as the combination of complete response, partial response (PR), and stable disease lasting at least 6 months. Only 1 of 7 patients with MF had CBR (ongoing PR &amp;gt; 18 months). CBR among the PTCL cases (n = 45) in cohorts 1, 2, and 3 were 53%, 45%, and 13% (cohorts 1 &amp; 2 vs 3, P = .02), respectively. Eight patients had CBR &amp;gt; 12 months (5 ongoing), including 4 of 5 patients with T-cell large granular lymphocytic leukemia. In an exploratory analysis using multiplex immunofluorescence, expression of phosphorylated S6, a marker of PI3 kinase or mitogen-activated protein kinase activation, in &amp;lt;25% of tumor cells was associated with response to ruxolitinib (P = .05). Our findings indicate that ruxolitinib is active across various PTCL subtypes and support a precision therapy approach to JAK\/STAT inhibition in patients with PTCL. This trial was registered at www.clincialtrials.gov as #NCT02974647.<\/jats:p>","DOI":"10.1182\/blood.2021013379","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T13:54:47Z","timestamp":1634738087000},"page":"2828-2837","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":198,"title":["A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK\/STAT targeting in T-cell lymphomas"],"prefix":"10.1182","volume":"138","author":[{"given":"Alison J.","family":"Moskowitz","sequence":"first","affiliation":[{"name":"Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY;"},{"name":"Department of Medicine, Weill Cornell Medical Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ghione","sequence":"additional","affiliation":[{"name":"Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, 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