蕈样真菌病
中央控制室4
医学
淋巴瘤
癌症研究
免疫学
免疫系统
趋化因子受体
趋化因子
作者
Sara Beygi,George E. Durán,Sebastian Fernandez‐Pol,Alain H. Rook,Youn H Kim,Michael S. Khodadoust
出处
期刊:Blood
[American Society of Hematology]
日期:2022-06-30
卷期号:139 (26): 3732-3736
被引量:17
标识
DOI:10.1182/blood.2021014468
摘要
Mogamulizumab is a humanized anti-CC chemokine receptor 4 (CCR4) antibody approved for the treatment of mycosis fungoides and Sézary syndrome. Despite almost universal expression of CCR4 in these diseases, most patients eventually develop resistance to mogamulizumab. We tested whether resistance to mogamulizumab is associated with loss of CCR4 expression. We identified 17 patients with mycosis fungoides or Sézary syndrome who either were intrinsically resistant or acquired resistance to mogamulizumab. Low expression of CCR4 by immunohistochemistry or flow cytometry was found in 65% of patients. Novel emergent CCR4 mutations targeting the N-terminal and transmembrane domains were found in 3 patients after disease progression. Emerging CCR4 copy number loss was detected in 2 patients with CCR4 mutations. Acquisition of CCR4 genomic alterations corresponded with loss of CCR4 antigen expression. We also report on outcomes of 3 cutaneous T-cell lymphoma (CTCL) patients with gain-of-function CCR4 mutations treated with mogamulizumab. Our study indicates that resistance to mogamulizumab in CTCL frequently involves loss of CCR4 expression and emergence of CCR4 genomic alterations. This finding has implications for management and monitoring of CTCL patients on mogamulizumab and development of future CCR4-directed therapies.
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