Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study.

By T. Ishida, T. Joh, N. Uike, Kazuhito Yamamoto, A. Utsunomiya, S. Yoshida, Y. Saburi, T. Miyamoto, S. Takemoto, H. Suzushima and 10 more. Journal of Clinical Oncology, 2012

622 citations recorded by the source corpus.

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.

Subfields: Agronomy and Crop Science, Ecology, Evolution, Behavior and Systematics, Immunology

View Paper: https://www.semanticscholar.org/paper/b37dd802edc0adb18f3f9490162fc13670369792

Citations in the corpus

• International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, neutral): “…IgG1 anti-CCR4 with defucosylation to enhance ADCC activity, was developed by Kyowa Hakko Kirin in Japan, and its clinical trials have been conducted against ATL and other peripheral T-cell lymphomas with highly promising results (Antoniu, 2010; Yamamoto et al., 2010; Ishida et al., 2012a).”