Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study.

Blood advances 2020 Oct 27

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Monitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696). Mogamulizumab-naive patients were enrolled (n = 102), of whom 101 received mogamulizumab-containing treatment (68 acute, 18 lymphoma, 12 chronic, and 3 smoldering subtypes). At enrollment, there was a significant inverse correlation between serum soluble interleukin-2 receptor (sIL-2R) levels and percentages of Tax-specific cytotoxic T lymphocytes (Tax-CTLs) in the entire lymphocyte population or in the CD8+ T cell subset, but there was not a correlation with cytomegalovirus pp65-specific cytotoxic T lymphocytes (CMV-CTLs). The overall response rate was 65%, and median progression-free survival and overall survival (OS) were 7.4 and 16.0 months, respectively. A higher percentage of Tax-CTLs, but not CMV-CTLs, within the entire lymphocyte population or in the CD8+ T cell subset was significantly associated with longer survival. Multivariate analysis identified the clinical subtype (acute or lymphoma type), a higher sIL-2R level, and a lower percentage of CD2-CD19+ B cells in peripheral blood mononuclear cells as significant independent unfavorable prognostic factors for OS. This indicates that a higher percentage of B cells might reflect some aspect of a favorable immune status leading to a good outcome with mogamulizumab treatment. In conclusion, the MIMOGA study has demonstrated that mogamulizumab exerts clinically meaningful antitumor activity in ATL. The patient's immunological status before mogamulizumab was significantly associated with treatment outcome. Further time series immunological analyses, in addition to comprehensive genomic analyses, are warranted. © 2020 by The American Society of Hematology.

Citation

Kentaro Yonekura, Shigeru Kusumoto, Ilseung Choi, Nobuaki Nakano, Asahi Ito, Youko Suehiro, Yoshitaka Imaizumi, Makoto Yoshimitsu, Kisato Nosaka, Eiichi Ohtsuka, Michihiro Hidaka, Tatsuro Jo, Hidenori Sasaki, Yukiyoshi Moriuchi, Masao Ogata, Hiro Tatetsu, Kenji Ishitsuka, Yasushi Miyazaki, Ryuzo Ueda, Atae Utsunomiya, Takashi Ishida. Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study. Blood advances. 2020 Oct 27;4(20):5133-5145