{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:01:59Z","timestamp":1779350519791,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100022274","name":"Daiichi Sankyo Europe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016348","name":"Kyowa Kirin Pharmaceutical Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>There is no standard of care in relapsed\/refractory T\u2010cell\/natural killer\u2010cell lymphomas. Patients often cycle through cytotoxic chemotherapy (CC), epigenetic modifiers (EM) or small molecule inhibitors (SMI) empirically. Ideal therapy at each line remains unknown. We conducted a retrospective, multiple intervention, \u2018target\u2010trial\u2019 using the PETAL global cohort. Patients received front\u2010line CC, then second and third line (2L and 3L) with either CC again, EM or SMI (12 possible treatment scenarios). Overall survival (OS; 2L or 3L to death) was compared across treatment sequences using Cox, reinforcement learning and synthetic intervention methods adjusting for age, histology, primary refractory disease, prognostic index for T\u2010cell lymphoma (PIT) score, response to 2L, and receipt of 2L transplant consolidation. Five hundred and forty received 2L (EM\u2009=\u2009101, SMI\u2009=\u200945, CC\u2009=\u2009394), and 290 received 3L (EM\u2009=\u200965, SMI\u2009=\u200944, CC\u2009=\u2009181). 2L SMI then 3L EM improved OS (adjusted hazard ratio [aHR]: 0.29, 95% confidence interval [CI]: 0.11\u20130.74; <jats:italic>p<\/jats:italic>\u2009=\u20090.010) versus 2L\u20133L CC\u2013CC, and consistently across most other sequential strategies. In 2L stability analyses, benefit was notable with 2L SMI in angioimmunoblastic T\u2010cell lymphoma (vs. CC: aHR: 0.23, 95% CI: 0.10\u20130.4; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001); vs. EM: aHR: 0.32, 95% CI: 0.12\u20130.82; <jats:italic>p<\/jats:italic>\u2009=\u20090.020), and both SMI and EM in PIT\u2010stratified high\u2010risk groups (SMI: aHR: 0.40, 95% CI: 0.21\u20130.76; <jats:italic>p<\/jats:italic>\u2009=\u20090.005; EM: aHR: 0.60, 95% CI: 0.39\u20130.92; <jats:italic>p<\/jats:italic>\u2009=\u20090.020) versus 2L CC. Results were consistent across all other independent stability and causal inference analyses providing a treatment selection framework.<\/jats:p>","DOI":"10.1111\/bjh.20063","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T11:00:43Z","timestamp":1746097243000},"page":"1664-1677","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Forecasting optimal treatments in relapsed\/refractory mature T\u2010 and <scp>NK<\/scp>\u2010cell lymphomas: A global <scp>PETAL<\/scp> Consortium study"],"prefix":"10.1111","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6906-0568","authenticated-orcid":false,"given":"Mark N.","family":"Sorial","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"},{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessy Xinyi","family":"Han","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Jung","family":"Koh","sequence":"additional","affiliation":[{"name":"Georgetown University School of Medicine  Washington, DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leora","family":"Boussi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junwei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew M.","family":"Lei","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline T.","family":"MacVicar","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Freydman","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Malespini","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenechukwu 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