{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:51:53Z","timestamp":1793055113012,"version":"4.5.0"},"reference-count":35,"publisher":"American Society of Hematology","issue":"10","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adult T-cell leukemia\/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. We evaluated the efficacy and safety of valemetostat, a potent enhancer of zeste homolog 2\u00a0(EZH2) and EZH1 inhibitor, in treating relapsed or refractory (R\/R) ATL. This multicenter phase 2 trial enrolled patients with R\/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Patients received valemetostat 200 mg\/day orally until progressive disease or unacceptable toxicity. The primary end point was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Secondary end points included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Twenty-five patients (median age, 69.0 years) with a median of 3\u00a0prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. The primary end point was met with a centrally reviewed ORR of 48.0% (90% confidence interval [CI], 30.5-65.9), including 5 complete and 7 partial remissions. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). IEAC-assessed median DOR was not\u00a0reached (NR) (95% CI, 1.87 to NR; months). Treatment-emergent adverse events (TEAEs) were manageable. TEAEs that occurred in \u226520% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Grade \u22653 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Valemetostat demonstrated promising efficacy and tolerability in heavily\u00a0pretreated patients, warranting further investigation in treating R\/R ATL. This trial was registered at www.clinicaltrials.gov as #NCT04102150.<\/jats:p>","DOI":"10.1182\/blood.2022016862","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T16:29:29Z","timestamp":1663950569000},"page":"1159-1168","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":162,"title":["An open-label, single-arm phase 2 trial of\u00a0valemetostat\u00a0for relapsed or refractory adult T-cell\u00a0leukemia\/lymphoma"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8057","authenticated-orcid":false,"given":"Koji","family":"Izutsu","sequence":"first","affiliation":[{"name":"1Department of Hematology, National Cancer Center Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-8088","authenticated-orcid":false,"given":"Shinichi","family":"Makita","sequence":"additional","affiliation":[{"name":"1Department of Hematology, National Cancer Center Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-2451","authenticated-orcid":false,"given":"Kisato","family":"Nosaka","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University Hospital, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5935-0385","authenticated-orcid":false,"given":"Makoto","family":"Yoshimitsu","sequence":"additional","affiliation":[{"name":"3Department of Hematology and Rheumatology, Kagoshima University Hospital, Kagoshima, 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University of the Ryukyus, Nishihara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7219-5589","authenticated-orcid":false,"given":"Kunihiro","family":"Tsukasaki","sequence":"additional","affiliation":[{"name":"7Department of Hematology, International Medical Center, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-8756","authenticated-orcid":false,"given":"Toyotaka","family":"Kawamata","sequence":"additional","affiliation":[{"name":"8Department of Hematology\/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3922-7432","authenticated-orcid":false,"given":"Takaaki","family":"Ono","sequence":"additional","affiliation":[{"name":"9Department of Transfusion and Cell Therapy, Hamamatsu University 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