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

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

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1157-1163
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number11
DOIs
Publication statusPublished - Apr 10 2014

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CCR4 Receptors
Peripheral T-Cell Lymphoma
Cutaneous T-Cell Lymphoma
Antibodies
Disease-Free Survival
Safety
Survival
mogamulizumab
T-Cell Lymphoma
Fever

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

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

In: Journal of Clinical Oncology, Vol. 32, No. 11, 10.04.2014, p. 1157-1163.

Research output: Contribution to journalArticle

Ogura, M, Ishida, T, Inagaki, H, Yamamoto, K, Ueda, R, Hatake, K, Tobinai, K, Akinaga, S, Taniwaki, M, Ando, K, Fujimoto, K, Miyamoto, T, Uike, N, Tamura, K, Tanimoto, M, Tsukasaki, K, Tomonaga, M, Ishizawa, K & Suzumiya, J 2014, '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', Journal of Clinical Oncology, vol. 32, no. 11, pp. 1157-1163. https://doi.org/10.1200/JCO.2013.52.0924
Ogura, Michinori ; Ishida, Takashi ; Inagaki, Hiroshi ; Yamamoto, Kazuhito ; Ueda, Ryuzo ; Hatake, Kiyohiko ; Tobinai, Kensei ; Akinaga, Shiro ; Taniwaki, Masafumi ; Ando, Kiyoshi ; Fujimoto, Katsuya ; Miyamoto, Toshihiro ; Uike, Naokuni ; Tamura, Kazuo ; Tanimoto, Mitsune ; Tsukasaki, Kunihiro ; Tomonaga, Masao ; Ishizawa, Kenichi ; Suzumiya, Junji. / 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. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 11. pp. 1157-1163.
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abstract = "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.",
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T1 - 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

AU - Ogura, Michinori

AU - Ishida, Takashi

AU - Inagaki, Hiroshi

AU - Yamamoto, Kazuhito

AU - Ueda, Ryuzo

AU - Hatake, Kiyohiko

AU - Tobinai, Kensei

AU - Akinaga, Shiro

AU - Taniwaki, Masafumi

AU - Ando, Kiyoshi

AU - Fujimoto, Katsuya

AU - Miyamoto, Toshihiro

AU - Uike, Naokuni

AU - Tamura, Kazuo

AU - Tanimoto, Mitsune

AU - Tsukasaki, Kunihiro

AU - Tomonaga, Masao

AU - Ishizawa, Kenichi

AU - Suzumiya, Junji

PY - 2014/4/10

Y1 - 2014/4/10

N2 - 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.

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