{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:36:31Z","timestamp":1792589791954,"version":"4.5.0"},"reference-count":27,"publisher":"American Society of Hematology","issue":"16","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Peripheral T-cell lymphomas (PTCLs) are uniquely vulnerable to epigenetic modifiers. We demonstrated in vitro synergism between histone deacetylase inhibitors and DNA methyltransferase inhibitors in preclinical models of T-cell lymphoma. In a phase 1 trial, we found oral 5-azacytidine and romidepsin to be safe and effective, with lineage-selective activity among patients with relapsed\/refractory (R\/R) PTCL. Patients who were treatment na\u00efve or who had R\/R PTCL received azacytidine 300 mg once per day on days 1 to 14, and romidepsin 14 mg\/m2 on days 8, 15, and 22 every 35 days. The primary objective was overall response rate (ORR). Targeted next-generation sequencing was performed on tumor samples to correlate mutational profiles and response. Among 25 enrolled patients, the ORR and complete response rates were 61% and 48%, respectively. However, patients with T-follicular helper cell (tTFH) phenotype exhibited higher ORR (80%) and complete remission rate (67%). The most frequent grade 3 to 4 adverse events were thrombocytopenia (48%), neutropenia (40%), lymphopenia (32%), and anemia (16%). At a median follow-up of 13.5 months, the median progression-free survival, duration of response, and overall survival were 8.0 months, 20.3 months, and not reached, respectively. The median progression-free survival and overall survival were 8.0 months and 20.6 months, respectively, in patients with R\/R disease. Patients with tTFH enjoyed a particularly long median survival (median not reached). Responders harbored a higher average number of mutations in genes involved in DNA methylation and histone deacetylation. Combined azacytidine and romidepsin are highly active in PTCL patients and could serve as a platform for novel regimens in this disease. This trial was registered at www.clinicaltrials.gov as #NCT01998035.<\/jats:p>","DOI":"10.1182\/blood.2020009004","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T17:58:20Z","timestamp":1605031100000},"page":"2161-2170","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":192,"title":["Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study"],"prefix":"10.1182","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1531-3838","authenticated-orcid":false,"given":"Lorenzo","family":"Falchi","sequence":"first","affiliation":[{"name":"1Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, 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