Bispecific Antibodies in B-Cell Lymphomas: Mechanisms, Efficacy, Toxicity, and Management

TL;DR

Bispecific antibodies are a promising treatment for B-cell lymphomas, offering high response rates but requiring careful management of immune-related side effects.

Contribution

This review provides a comprehensive analysis of CD20 × CD3 bispecific antibodies, their mechanisms, efficacy, and toxicity management in B-cell lymphomas.

Findings

CD20 × CD3 bispecific antibodies show high overall and complete response rates in diffuse large B-cell and follicular lymphomas.

Immune-related toxicities like cytokine release syndrome and neurotoxicity are significant challenges with these therapies.

Prophylactic measures and immunoglobulin supplements are recommended to manage infection risks associated with bispecific antibody therapy.

Abstract

Bispecific antibodies represent a pivotal advancement in treating relapsed/refractory B-cell lymphomas, addressing unmet needs for patients with limited conventional options. This review examines CD20 × CD3 bispecific antibodies (BsAbs) like mosunetuzumab, epcoritamab, odronextamab, and glofitamab, which link malignant B-cells and T-cells, thus inducing targeted tumor lysis. These IgG-like molecules activate T-cells, triggering proliferation and cytotoxic molecule release, bypassing MHC presentation. These agents have received regulatory approval for the treatment of various B-cell lymphomas and exhibit substantial efficacy, with high overall and complete response rates in diffuse large B-cell lymphoma and follicular lymphoma. However, their use is associated with immune-related toxicities. Cytokine Release Syndrome, which is a systemic inflammatory response due to a cytokine surge, and Immune Effector Cell-Associated Neurotoxicity Syndrome, linked to endothelial activation and blood–brain barrier disruption, are critical concerns. This review details their mechanisms, grading, and management, including the use of tocilizumab and corticosteroids. Furthermore, BsAb therapy carries an elevated susceptibility to viral, bacterial, and opportunistic infections, often exacerbated by hypogammaglobulinemia. Expert recommendations for antimicrobial prophylaxis, including herpes and varicella zoster virus, pneumocystis, and immunoglobulin supplements are crucial for mitigating these risks. While BsAbs offer an “off-the-shelf” advantage, balancing their efficacy with comprehensive toxicity management is crucial for maximizing patient outcomes.

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