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


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.


CONCLUSIONS
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.
Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan. itakashi@med.nagoya-cu.ac.jp
Takashi
T
Ishida
Tatsuro
T
Joh
Naokuni
N
Uike
Kazuhito
K
Yamamoto
Atae
A
Utsunomiya
Shinichiro
S
Yoshida
Yoshio
Y
Saburi
Toshihiro
T
Miyamoto
Shigeki
S
Takemoto
Hitoshi
H
Suzushima
Kunihiro
K
Tsukasaki
Kisato
K
Nosaka
Hiroshi
H
Fujiwara
Kenji
K
Ishitsuka
Hiroshi
H
Inagaki
Michinori
M
Ogura
Shiro
S
Akinaga
Masao
M
Tomonaga
Kensei
K
Tobinai
Ryuzo
R
Ueda
D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000401:mortality; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000166:cytology; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; C549035:mogamulizumab