Antibody-drug conjugates: a practical review on clinical management of toxicities
Antonio De Palma1, Marco Marenco2, Sofia Mancini1
1Department of Maternal and Child Health and Gynecological Sciences, Sapienza University, Policlinico Umberto I, Rome, Italy.
Introduction:
Antibody-drug conjugates (ADCs) are rapidly expanding across solid tumors, but their toxicity profiles remain heterogeneous and clinically challenging. This review addresses the need for practical, standardized approaches to identifying and managing ADC-related adverse events.
Areas Covered:
We summarize the mechanisms underlying ADC toxicity, focusing on EMA-approved agents and their most frequent or severe adverse events, including ILD/pneumonitis, ocular toxicity, neutropenia, diarrhea, skin reactions, and hyperglycemia. We combine evidence from pivotal trials, regulatory documents, and emerging literature with practical clinical experience. The review includes operational algorithms and flowcharts designed to support real-world decision-making. Literature was identified through PubMed and EMBASE searches, regulatory Summary of Product Characteristics (SmPCs), and key phase I-III clinical trials up to January 2025.
Expert Opinion:
Improving ADC tolerability will require earlier identification of high-risk patients, structured toxicity-monitoring pathways, and molecular innovations such as Fc engineering, linker optimization, and probody or bispecific ADC formats. Integrating predictive tools, including AI-based radiomics, may further reduce toxicity and expand the therapeutic index.
Insights
This review provides practical strategies for managing adverse events associated with antibody-drug conjugates (ADCs) in solid tumors. It highlights mechanisms, common toxicities, and innovative approaches to improve patient tolerability and expand the therapeutic index of ADCs.
Area of Science:
- Oncology
- Pharmacology
- Clinical Medicine
Background:
- Antibody-drug conjugates (ADCs) show promise in solid tumors but present heterogeneous and challenging toxicity profiles.
- Standardized approaches are needed for identifying and managing adverse events related to ADCs.
Purpose of the Study:
- To review the mechanisms of ADC toxicity.
- To outline practical, standardized approaches for identifying and managing ADC-related adverse events.
- To discuss strategies for improving ADC tolerability.
Main Methods:
- Literature search of PubMed and EMBASE up to January 2025.
- Review of regulatory documents (SmPCs) and phase I-III clinical trials.
- Synthesis of evidence from trials, regulatory data, and clinical experience.
Main Results:
- Common ADC toxicities include interstitial lung disease (ILD)/pneumonitis, ocular toxicity, neutropenia, diarrhea, skin reactions, and hyperglycemia.
- Operational algorithms and flowcharts are provided for real-world decision-making.
- Evidence supports the need for early identification of high-risk patients and structured monitoring.
Conclusions:
- Improving ADC tolerability requires early risk identification, structured monitoring, and molecular innovations (e.g., Fc engineering, linker optimization).
- Predictive tools, including AI-based radiomics, may further reduce toxicity and enhance the therapeutic index of ADCs.
- Standardized management strategies are crucial for safe and effective ADC utilization in solid tumors.
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