Defucosylated Anti-CCR4 Monoclonal Antibody (KW-0761) for Relapsed Adult T-Cell Leukemia-Lymphoma: A Multicenter Phase II Study

作者：Ishida, Takashi^*; Joh, Tatsuro; Uike, Naokuni; Yamamoto, Kazuhito; Utsunomiya, Atae; Yoshida, Shinichiro; Saburi, Yoshio; Miyamoto, Toshihiro; Takemoto, Shigeki; Suzushima, Hitoshi; Tsukasaki, Kunihiro; Nosaka, Kisato; Fujiwara, Hiroshi; Ishitsuka, Kenji; Inagaki, Hiroshi; Ogura, Michinori; Akinaga, Shiro; Tomonaga, Masao; Tobinai, Kensei; Ueda, Ryuzo

来源：Journal of Clinical Oncology, 2012, 30(8): 837-842.

DOI：10.1200/JCO.2011.37.3472

• MOLECULAR TARGET
• LEUKEMIA/LYMPHOMA
• CCR4
• EXPRESSION
• CHEMOKINE
• IMMUNOTHERAPY
• ACTIVATION
• ZIDOVUDINE
• TRANSPLANTATION
• CYTOTOXICITY

Purpose @@@ Adult T-cell leukemia-lymphoma (ATL) is usually resistant to conventional chemotherapies, and there are few other treatment options. Because CC chemokine receptor 4 (CCR4) is expressed on tumor cells from most patients with ATL, KW-0761, a humanized anti-CCR4 monoclonal antibody, which markedly enhances antibody-dependent cellular cytotoxicity, was evaluated in the treatment of patients with relapsed ATL. @@@ Patients and Methods @@@ A multicenter phase II study of KW-0761 for patients with relapsed, aggressive CCR4-positive ATL was conducted to evaluate efficacy, pharmacokinetic profile, and safety. The primary end point was overall response rate, and secondary end points included progression-free and overall survival from the first dose of KW-0761. Patients received intravenous infusions of KW-0761 once per week for 8 weeks at a dose of 1.0 mg/kg. @@@ Results @@@ Of 28 patients enrolled onto the study, 27 received at least one infusion of KW-0761. Objective responses were noted in 13 of 26 evaluable patients, including eight complete responses, with an overall response rate of 50% (95% CI, 30% to 70%). Median progression-free and overall survival were 5.2 and 13.7 months, respectively. The mean half-life period after the eighth infusion was 422 +/- 147 hours (+/- standard deviation). The most common adverse events were infusion reactions (89%) and skin rashes (63%), which were manageable and reversible in all cases. @@@ Conclusion @@@ KW-0761 demonstrated clinically meaningful antitumor activity in patients with relapsed ATL, with an acceptable toxicity profile. Further investigation of KW-0761 for treatment of ATL and other T-cell neoplasms is warranted. J Clin Oncol 30: 837-842.

• 出版日期2012-3-10