Sequelae of B-Cell Depleting Therapy: An Immunologist's Perspective. [Review]

Kacar, M.; Al-Hakim, A.; Savic, S.

Sequelae of B-Cell Depleting Therapy: An Immunologist's Perspective. [Review]

All Authors

Kacar, M.

Al-Hakim, A.

Savic, S.

LTHT Author

Kacar, Mark
Al-Hakim, Adam
Savic, Sinisa
Savic, Sinisa

LTHT Department

Clinical Immunology & Allergy
NIHR Leeds Biomedical Research Centre

Publication Date

2025

Item Type

Journal Article
Review

Abstract

B-cell depleting therapy (BCDT) has revolutionised the treatment of B-cell malignancies and autoimmune diseases by targeting specific B-cell surface antigens, receptors, ligands, and signalling pathways. This narrative review explores the mechanisms, applications, and complications of BCDT, focusing on the therapeutic advancements since the introduction of rituximab in 1997. Various monoclonal antibodies and kinase inhibitors are examined for their roles in depleting B cells through antibody-dependent and independent mechanisms. The off-target effects, such as hypogammaglobulinemia, infections, and cytokine release syndrome, are discussed, emphasising the need for immunologists to identify and help manage these complications. The increasing prevalence of BCDT has necessitated the involvement of clinical immunologists in addressing treatment-associated immunological abnormalities, including persistent hypogammaglobulinemia and neutropenia. We highlight the importance of considering underlying inborn errors of immunity (IEI) in patients presenting with these complications. Furthermore, we discuss the impact of BCDT on other immune cell populations and the challenges in predicting and managing long-term immunological sequelae. The potential for novel BCDT agents targeting the BAFF/APRIL-TACI/BCMA axis and B-cell receptor signalling pathways to treat autoimmune disorders is also explored, underscoring the rapidly evolving landscape of B-cell targeted therapies.