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【Research News】CCR4 mutations associated with superior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment

July 17,2018

Adult T-cell leukemia/lymphoma (ATL) has a dismal prognosis. Because CCR4 is expressed on tumor cells from most ATL patients, a therapeutic anti-CCR4 monoclonal antibody, mogamulizumab, has been developed. Herein, the mutations in the carboxyl terminus of CCR4 were observed in 38 (33%) of the 116 ATL patients, and these CCR4 mutations should be a gain-of-function phenotype. There was no significant difference in the overall survival in the all ATL patients according to the CCR4 mutations. On the other hand, in the ATL patients, who received the mogamulizumab-containing treatment but not an allogeneic hematopoietic stem cell transplantation (HSCT), survival rate at 5-year from the day of the first dose of mogamulizumab with (n = 11) or without (n = 31) the CCR4 mutations were 72.7% and 26.2%, respectively (P = 0.027). In addition, in the patients with aggressive variant, survival rate at 5-year from the day of the first dose of mogamulizumab with (n = 10) or without (n = 28) the CCR4 mutations were 80.0% and 24.7%, respectively (P = 0.006). These findings indicate that ATL patients with the CCR4 mutations are special responders to the mogamulizumab-containing treatment. In conclusion, the CCR4 gain-of-function mutations determine the sensitivity to mogamulizumab in ATL.

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Published online Date:June 22,2018

Journal:Blood. DOI: 10.1182/blood-2018-02-835991,
PMID: 29930010

Title CCR4 mutations associated with superior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment
Author Yuma Sakamoto, Takashi Ishida,Ayako Masaki,Takayuki Murase,Kentaro Yonekura,Yukie Tashiro,Masahito Tokunaga,Atae Utsunomiya,Asahi Ito,Shigeru Kusumoto,Shinsuke Iida,Ryuzo Ueda,Hiroshi Inagaki,equally contributed
Article URL http://www.bloodjournal.org/content/early/2018/06/20/blood-2018-02-835991
Researcher URL

http://www.med.nagoya-cu.ac.jp/patho2.dir/mysite1/index.html

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