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An updated perspective on immunoglobulin replacement in chronic lymphocytic leukaemia in the era of targeted therapies

Khan, Sujoy; Allsup, David; Molica, Stefano

Authors

Sujoy Khan

Stefano Molica



Abstract

Chronic lymphocytic leukaemia (CLL) is a malignancy of clonally expanded antigen-switched, neoplastic, mature B cells. CLL is characterised by a variable degree of immunosuppression and secondary hypogammaglobulinemia. B-cell depleting therapies have historically been deployed with a proportion of patients becoming resistant to multiple lines of treatment with an associated worsening of immunosuppression and heightened infection risk. Advances in molecular diagnostics and the development of new therapies targeting Bruton’s tyrosine kinase and B-cell lymphoma-2 have resulted in novel insights into the cellular mechanisms associated with an increased infection risk and T-cell escape from the complex tumour environment found in CLL. Generally, immunoglobulin replacement therapy with polyvalent human immunoglobulin G (IgG) is indicated in patients with recurrent severe bacterial infections and low IgG levels, but there is no consensus on the threshold IgG level for initiation of such therapy. A proportion of CLL patients have residual IgG production, with preserved quality of the immunoglobulin molecules, and therefore a definition of ‘IgG quality’ may allow for lower dosing or less frequent treatment with immunoglobulin therapy in such patients. Immunoglobulin therapy can restore innate immunity and in conjunction with CLL targeted therapies may allow T-cell antigen priming, restore T-cell function thereby providing an escape from tumour-associated autoimmunity and the development of an immune-mediated anti-tumour effect. This review aims to discuss the mechanisms by which CLL-targeted therapy may exert a synergistic therapeutic effect with immunoglobulin replacement therapy both in terms of reducing tumour bulk and restoration of immune function.

Citation

Khan, S., Allsup, D., & Molica, S. (2023). An updated perspective on immunoglobulin replacement in chronic lymphocytic leukaemia in the era of targeted therapies. Frontiers in Oncology, 13, Article 1135812. https://doi.org/10.3389/fonc.2023.1135812

Journal Article Type Review
Acceptance Date Mar 27, 2023
Online Publication Date Apr 6, 2023
Publication Date Apr 6, 2023
Deposit Date Apr 6, 2023
Publicly Available Date Apr 14, 2023
Journal Frontiers in Oncology
Electronic ISSN 2234-943X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 13
Article Number 1135812
DOI https://doi.org/10.3389/fonc.2023.1135812
Keywords CLL; Hypogammaglobulinemia; Ig replacement; Immunomodulation; Restoration immunity
Public URL https://hull-repository.worktribe.com/output/4255894

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
Copyright © 2023 Khan, Allsup and Molica. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.





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