title: Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma.
abstract: OBJECTIVE
  CC chemokine receptor 4 (CCR4) is expressed by peripheral T-cell lymphomas (PTCLs) and is associated with poor outcomes. Mogamulizumab (KW-0761) is a defucosylated humanized anti-CCR4 antibody engineered to exert potent antibody-dependent cellular cytotoxicity. This multicenter phase II study evaluated the efficacy and safety of mogamulizumab in patients with relapsed PTCL and cutaneous T-cell lymphoma (CTCL).
  
  
  METHODS
  Mogamulizumab (1.0 mg/kg) was administered intravenously once per week for 8 weeks to patients with relapsed CCR4-positive PTCL or CTCL. The primary end point was the overall response rate, and the secondary end points included safety, progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  A total of 38 patients were enrolled, and 37 patients received mogamulizumab. Objective responses were noted for 13 of 37 patients (35%; 95% CI, 20% to 53%), including five patients (14%) with complete response. The median PFS was 3.0 months (95% CI, 1.6 to 4.9 months), and the median OS was not calculated. The mean maximum and trough mogamulizumab concentrations (± standard deviation) after the eighth infusion were 45.9 ± 9.3 and 29.0 ± 13.3 μg/mL, respectively. The most common adverse events were hematologic events, pyrexia, and skin disorders, all of which were reversible and manageable.
  
  
  CONCLUSIONS
  Mogamulizumab exhibited clinically meaningful antitumor activity in patients with relapsed PTCL and CTCL, with an acceptable toxicity profile. Further investigation of mogamulizumab for treatment of T-cell lymphoma is warranted.
authors.affiliation: Michinori Ogura, Nagoya Daini Red Cross Hospital; Takashi Ishida and Hiroshi Inagaki, Nagoya City University Graduate School of Medical Sciences; Kazuhito Yamamoto, Aichi Cancer Center; Ryuzo Ueda, Aichi Medical University School of Medicine, Nagoya; Kiyohiko Hatake, Japanese Foundation for Cancer Research; Kensei Tobinai, National Cancer Center Hospital; Shiro Akinaga, Kyowa Hakko Kirin, Tokyo; Masafumi Taniwaki, Kyoto Prefectural University of Medicine, Kyoto; Kiyoshi Ando, Tokai University School of Medicine, Kanagawa; Katsuya Fujimoto, Hokkaido University Graduate School of Medicine, Sapporo; Toshihiro Miyamoto, Kyushu University Graduate School of Medical Sciences; Naokuni Uike, National Hospital Organization Kyushu Cancer Center; Kazuo Tamura, Fukuoka University, Fukuoka; Mitsune Tanimoto, Okayama University Hospital, Okayama; Kunihiro Tsukasaki, Nagasaki University Graduate School of Biomedical Science; Masao Tomonaga, Japanese Red Cross Nagasaki Atomic Bomb Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Sendai; and Junji Suzumiya, Shimane University Hospital, Izumo, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Katsuya
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsukasaki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Akinaga
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007564:Japan; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D054398:Receptors, CCR4; C549035:mogamulizumab