Antibody-drug conjugates: a practical review on clinical management of toxicities.

Abstract

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.