Antibody–drug conjugates in B-cell lymphomas: current evidence and future directions

Alexandros Angelopoulos*

* Faculty of Medicine, School of Cancer Sciences, Centre for Cancer Immunology, University of Southampton, SO16 6YD

Pages: 13-21 ⏐ Published: 15 Jan 2026 ⏐ DOI: https://doi.org/10.70145/MeSh0004

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B-cell lymphomas represent a heterogeneous subset of non-Hodgkin lymphomas, with aggressive and indolent subtypes frequently treated first-line with rituximab-based chemotherapy. Relapsed or refractory (R/R) disease remains a major clinical challenge, particularly in patients progressing after chimeric antigen receptor (CAR) T-cell therapy, who experience poor survival outcomes. Antibody–drug conjugates (ADCs) have emerged as a promising therapeutic approach, combining the specificity of monoclonal antibodies with cytotoxic payloads to enhance anti-tumour efficacy while limiting systemic toxicity. This review provides a systematic overview of clinical development of ADCs in B-cell lymphomas, focusing on completed Phase II–IV trials. A total of 119 clinical trials were identified, with 36 completed studies informing the most clinically relevant evidence. ADCs targeting CD19, CD22, CD30, and CD79b have demonstrated meaningful anti-tumour activity, with loncastuximab tesirine and polatuzumab vedotin showing particularly durable responses and manageable safety profiles. However, response rates vary across targets, highlighting the importance of antigen selection, expression, and disease biology. Toxicities such as myelosuppression, hepatotoxicity, peripheral neuropathy, and post-transplant complications remain key considerations. Despite progress, gaps persist in underrepresented B-cell lymphoma subtypes and unexplored antigen targets, as well as in strategies to optimise durability of response. Future development may benefit from biomarker-driven patient stratification, rational combination therapies, and innovations in ADC design to maximise efficacy and safety. Overall, ADCs are establishing a significant role in the management of R/R B-cell lymphomas, and ongoing efforts are essential to fully realise their therapeutic potential.

Keywords: B-cell lymphoma, antibody–drug conjugates, relapsed disease, targeted therapy, clinical trials

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