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

Br J Haematol. 2022 Feb;196(3):629-638. doi: 10.1111/bjh.17895. Epub 2021 Oct 10.

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.

Keywords: adult T-cell leukaemia-lymphoma; immunoglobulin G B-cell diversity; mogamulizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / mortality
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis
  • Treatment Outcome

Substances

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