Immunohistochemistry for CCR4 C-terminus predicts CCR4 mutations and mogamulizumab efficacy in adult T-cell leukemia/lymphoma.

Abstract

Mogamulizumab targets extracellular N-terminal domain of CCR4, which is expressed in most adult T-cell leukemia/lymphoma (ATL) cases. Recently, we reported that CCR4 C-terminal gain-of-function mutations were frequent in ATL cases, and a subgroup with these mutations who were treated without allogenic hematopoietic stem cell transplantation (HSCT) and with mogamulizumab-containing [HSCT (-) and mogamulizumab (+)] regimens had a superior survival rate. Although these mutations are most likely a biomarker for predicting a strong response to mogamulizumab, their detection is time-consuming and costly. A more convenient screening tool may be necessary in the clinical setting. In this study, the clinicopathological importance of immunohistochemistry for the CCR4 N-terminus (CCR4-N-IHC) and C-terminus (CCR4-C-IHC) was examined in a large ATL cohort (n = 92). We found that CCR4-C-IHC, but not CCR4-N-IHC, was inversely correlated with the CCR4 mutation status. In ATL patients negative for CCR4-C-IHC, a subgroup treated with HSCT (-) and mogamulizumab (+) regimens showed a significantly better prognosis. In addition, CCR4-C-IHC was found to be a useful marker for high-sensitivity screening of the CCR4 mutational status (87%). The present study suggests that CCR4-C-IHC may be useful for identifying ATL patients harboring mutated CCR4 who may benefit from the superior efficacy of mogamulizumab-containing regimens and that CCR4-C-IHC may be a rapid and cost-efficient tool for screening for CCR4 mutation status.

• Authors: Keiichiro Fujii, Yuma Sakamoto, Ayako Masaki, Takayuki Murase, Yukie Tashiro, Kentaro Yonekura, Atae Utsunomiya, Asahi Ito, Shigeru Kusumoto, Shinsuke Iida, Ryuzo Ueda, Takashi Ishida, Hiroshi Inagaki
• Journal: The journal of pathology. Clinical research (J Pathol Clin Res) Vol. 7 Issue 1 Pg. 52-60 (01 2021) ISSN: 2056-4538 [Electronic] England
• PMID: 33022137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• Biomarkers, Tumor
• CCR4 protein, human
• Receptors, CCR4
• mogamulizumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents, Immunological (therapeutic use)
• Biomarkers, Tumor (genetics)
• Clinical Decision-Making
• DNA Mutational Analysis
• Female
• Humans
• Immunohistochemistry
• Leukemia-Lymphoma, Adult T-Cell (drug therapy, genetics, immunology)
• Male
• Mutation
• Patient Selection
• Predictive Value of Tests
• Protein Domains
• Receptors, CCR4 (antagonists & inhibitors, genetics)
• Treatment Outcome