{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:18:50Z","timestamp":1790745530181,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>PTCL with T-follicular helper phenotype (PTCL-TFH) has recurrent mutations affecting epigenetic regulators, which may contribute to aberrant DNA methylation and chemoresistance. This phase 2 study evaluated oral azacitidine (CC-486), a DNA methyltransferase inhibitor, plus CHOP as initial treatment for PTCL (ClinicalTrials.gov - NCT03542266). CC-486 at 300 mg daily was administered for 7 days prior to C1 of CHOP, and for 14 days before CHOP C2-6. The primary endpoint was end-of-treatment CR. Secondary endpoints included ORR, safety and survival. Correlative studies assessed mutations, gene expression and methylation in tumor samples. Grade 3-4 hematologic toxicities were mostly neutropenia (71%), with febrile neutropenia uncommon (14%). Non-hematologic toxicities included fatigue (14%) and GI symptoms (5%). In 20 evaluable patients, CR was 75%, including 88.2% for PTCL-TFH (n=17). At a median follow-up of 21 months, 2-yr PFS was 65.8% for all and 69.2% for PTCL-TFH, while 2-yr OS was 68.4% for all and 76.1% for PTCL-TFH. The frequencies of the TET2, RHOA, DNMT3A, and IDH2 mutations were 76.5%, 41.1%, 23.5% and 23.5%, respectively, with TET2 mutations significantly associated with CR (p=0.007), favorable PFS (p=0.004) and OS (p=0.015), and DNMT3A mutations associated with adverse PFS (p=0.016). CC-486 priming contributed to the reprograming of the tumor microenvironment by upregulation of genes related to apoptosis (p&amp;lt;0.01) and inflammation (p&amp;lt;0.01). DNA methylation did not show significant shift. This safe and active initial therapy regimen is being further evaluated in the ALLIANCE randomized study A051902 in CD30-negative PTCL.<\/jats:p>","DOI":"10.1182\/blood.2022018254","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T21:17:05Z","timestamp":1676582225000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":36,"title":["Multicenter Phase 2 Study of Oral azacitidine (CC-486) plus CHOP as initial treatment for peripheral T-cell lymphoma"],"prefix":"10.1182","author":[{"given":"Jia","family":"Ruan","sequence":"first","affiliation":[{"name":"Weill Cornell Medicine, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison J","family":"Moskowitz","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York, United 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Presbyterian Hospital, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0608-1350","authenticated-orcid":false,"given":"Leandro","family":"Cerchietti","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Martin","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College, New York, New York, United 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