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

作者：Ogura, Michinori^*; Ishida, Takashi; Hatake, Kiyohiko; Taniwaki, Masafumi; Ando, Kiyoshi; Tobinai, Kensei; Fujimoto, Katsuya; Yamamoto, Kazuhito; Miyamoto, Toshihiro; Uike, Naokuni; Tanimoto, Mitsune; Tsukasaki, Kunihiro; Ishizawa, Kenichi; Suzumiya, Junji; Inagaki, Hiroshi; Tamura, Kazuo; Akinaga, Shiro; Tomonaga, Masao; Ueda, Ryuzo

来源：Journal of Clinical Oncology, 2014, 32(11): 1157-+.

DOI：10.1200/JCO.2013.52.0924

• MYCOSIS-FUNGOIDES
• SEZARY-SYNDROME
• EUROPEAN-ORGANIZATION
• INTERNATIONAL-SOCIETY
• CONSENSUS STATEMENT
• LEUKEMIA-LYMPHOMA
• RESPONSE CRITERIA
• TASK-FORCE
• EXPRESSION
• TRIAL

Purpose 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). @@@ Patients and 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 g/mL, respectively. The most common adverse events were hematologic events, pyrexia, and skin disorders, all of which were reversible and manageable. @@@ Conclusion 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. J Clin Oncol 32:1157-1163.

• 出版日期2014-4-10