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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.
J Clin Oncol 2014; 32(11):1157-63JC

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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24616310

Citation

Ogura, Michinori, et al. "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 : Official Journal of the American Society of Clinical Oncology, vol. 32, no. 11, 2014, pp. 1157-63.
Ogura M, Ishida T, Hatake K, et al. 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. J Clin Oncol. 2014;32(11):1157-63.
Ogura, M., Ishida, T., Hatake, K., Taniwaki, M., Ando, K., Tobinai, K., ... Ueda, R. (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 : Official Journal of the American Society of Clinical Oncology, 32(11), pp. 1157-63. doi:10.1200/JCO.2013.52.0924.
Ogura M, et al. 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. J Clin Oncol. 2014 Apr 10;32(11):1157-63. PubMed PMID: 24616310.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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 - Hatake,Kiyohiko, AU - Taniwaki,Masafumi, AU - Ando,Kiyoshi, AU - Tobinai,Kensei, AU - Fujimoto,Katsuya, AU - Yamamoto,Kazuhito, AU - Miyamoto,Toshihiro, AU - Uike,Naokuni, AU - Tanimoto,Mitsune, AU - Tsukasaki,Kunihiro, AU - Ishizawa,Kenichi, AU - Suzumiya,Junji, AU - Inagaki,Hiroshi, AU - Tamura,Kazuo, AU - Akinaga,Shiro, AU - Tomonaga,Masao, AU - Ueda,Ryuzo, Y1 - 2014/03/10/ PY - 2014/3/12/entrez PY - 2014/3/13/pubmed PY - 2014/6/6/medline SP - 1157 EP - 63 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 32 IS - 11 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. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/24616310/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_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2013.52.0924?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -