title: Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma.
abstract: BACKGROUND
  Chidamide is a novel benzamide type of subtype-selective histone deacetylase (HDAC) inhibitor with unique mechanisms of action compared with marketed HDAC inhibitors. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL) in Chinese population.
  
  
  METHODS
  Patients with relapsed or refractory PTCL of different subtypes received chidamide of 30 mg orally twice per week. The primary end point was overall response rate (ORR). Responding patients should be confirmed at least 4 weeks after the criteria of the response were first met, and were reviewed by an independent review committee.
  
  
  RESULTS
  Eighty-three patients were enrolled and 79 patients with eligible PTCL histology were for efficacy assessments. Patients enrolled over 10% were with subtypes of PTCL not otherwise specified (34%), anaplastic large-cell lymphoma (22%), extranodal natural killer (NK)/T-cell lymphoma, nasal type (20%), or angioimmunoblastic T-cell lymphoma (AITL, 13%). The ORR was 28% (22 of 79) including 14% (11 of 79) with complete response/unconfirmed complete response (CR/CRu). Median progression-free survival and overall survival were 2.1 and 21.4 months, respectively. AITL patients tended to have higher ORR (50%) and CR/CRu rate (40%), as well as more durable responses, to chidamide treatment. Most adverse events (AEs) were grade 1 or 2, and AEs ≥grade 3 that occurred in ≥10% patients were thrombocytopenia (22%), leucopenia (13%) and neutropenia (11%), respectively.
  
  
  CONCLUSIONS
  Chidamide represents a novel oral benzamide class of HDAC inhibitor with significant single-agent activity and manageable toxicity in relapsed or refractory PTCL, and provides a much needed treatment option in this indication in China. Results led to China Food and Drug Administration approval of chidamide in this indication.
authors.affiliation: Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing syuankai@cicams.ac.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing.
authors.forename: M
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai.
authors.forename: X
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Lymphoma, 307 Hospital of PLA, Beijing.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing.
authors.forename: J
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, Beijing Caner Hospital, Beijing.
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Hematology, Peking University Third Hospital, Beijing.
authors.forename: X
authors.initials: X
authors.lastname: Ke
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou.
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Hematology, Ruijin Hospital/Medical College, Shanghai Jiao Tong University, Shanghai.
authors.forename: Z
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou.
authors.forename: Y
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Hematology, the First Hospital, Jilin University, Changchun.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Hematology, Xiangya Hospital Central South University, Changsha.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Lymphoma, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin.
authors.forename: J
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Hematology, the First Affiliated Hospital, Zhejiang University, Hangzhou.
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing.
authors.forename: D
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Chipscreen Biosciences Ltd, Shenzhen, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Chipscreen Biosciences Ltd, Shenzhen, China.
authors.forename: X
authors.initials: X
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D018572:Disease-Free Survival; D058527:Enteropathy-Associated T-Cell Lymphoma / Q000188:drug therapy; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D054391:Lymphoma, Extranodal NK-T-Cell / Q000188:drug therapy; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D012878:Skin Neoplasms / Q000188:drug therapy; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; C547816:N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
keywords: HDAC inhibitor; T-cell lymphoma; chidamide; epigenetic; pivotal trial