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

• DOI: 10.1200/jco.2013.52.0924
• Publication Date: 2014-03-11T04:24:17Z
• Authors: Michinori Ogura; Takashi Ishida; Kiyohiko Hatake; Masafumi Taniwaki; Kiyoshi Ando; Kensei Tobinai; Katsuya Fujimoto; Kazuhito Yamamoto; Toshihiro Miyamoto; Naokuni Uike; Mitsune Tanimoto; Kunihiro Tsukasaki; Kenichi Ishizawa; Junji Suzumiya; Hiroshi Inagaki; Kazuo Tamura; Shiro Akinaga; Masao Tomonaga; Ryuzo Ueda
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Receptors, CCR4; Lymphoma, T-Cell, Peripheral; Middle Aged; Antibodies, Monoclonal, Humanized; Lymphoma, T-Cell, Cutaneous; 3. Good health; Survival Rate; 03 medical and health sciences; Treatment Outcome; Japan; Humans; Female; Neoplasm Recurrence, Local; Aged

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 μg/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.