Clinical significance of the immunoglobulin G heavy-chain repertoire in peripheral blood mononuclear cells of adult T-cell leukaemia-lymphoma patients receiving mogamulizumab.

Abstract

'Monitoring of immune responses following mogamulizumab-containing treatment in patients with adult T-cell leukaemia-lymphoma (ATL)' (MIMOGA) is a multicentre prospective clinical study (UMIN000008696). In the MIMOGA study, we found that a lower percentage of CD2- CD19+ B cells in peripheral blood mononuclear cells (PBMC) was a significant unfavourable prognostic factor for overall survival (OS). Accordingly, we then analysed the immunoglobulin G (IgG) heavy-chain repertoire in PBMC by high-throughput sequencing. Of the 101 patients enrolled in the MIMOGA study, for 81 a sufficient amount of PBMC RNA was available for repertoire sequencing analysis. Peripheral IgG B cells in patients with ATL had a restricted repertoire relative to those in healthy individuals. There was a significant positive correlation between the Shannon-Weaver diversity index (SWDI) for the IgG repertoire and proportions of B cells in the PBMC of the patients. Multivariate analysis identified two variables significantly affecting OS: a higher serum soluble interleukin-2 receptor level, and a lower SWDI for the IgG repertoire [hazard ratio, 2·124; 95% confidence interval, 1·114-4·049; n = 44]. The present study documents the importance of humoral immune responses in patients receiving mogamulizumab-containing treatment. Further investigation of strategies to enhance humoral immune responses in patients with ATL is warranted.

• Authors: Kisato Nosaka, Shigeru Kusumoto, Nobuaki Nakano, Ilseung Choi, Makoto Yoshimitsu, Yoshitaka Imaizumi, Michihiro Hidaka, Hidenori Sasaki, Junya Makiyama, Eiichi Ohtsuka, Tatsuro Jo, Masao Ogata, Asahi Ito, Kentaro Yonekura, Hiro Tatetsu, Takeharu Kato, Toshiro Kawakita, Youko Suehiro, Kenji Ishitsuka, Shinsuke Iida, Takaji Matsutani, Atae Utsunomiya, Ryuzo Ueda, Takashi Ishida
• Journal: British journal of haematology (Br J Haematol) Vol. 196 Issue 3 Pg. 629-638 (02 2022) ISSN: 1365-2141 [Electronic] England
• PMID: 34632569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• Biomarkers, Tumor
• Circulating Tumor DNA
• Immunoglobulin G
• Immunoglobulin Heavy Chains
• mogamulizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents, Immunological (therapeutic use)
• Biomarkers, Tumor
• Circulating Tumor DNA
• Female
• Genetic Variation
• Humans
• Immunoglobulin G (genetics)
• Immunoglobulin Heavy Chains (genetics)
• Leukemia-Lymphoma, Adult T-Cell (blood, drug therapy, genetics, mortality)
• Leukocytes, Mononuclear (metabolism)
• Male
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Survival Analysis
• Treatment Outcome