Risk-Stratified Management of ADC drug-Related Neutropenia: Integrating Clinical Trial Meta-Summary and Existing Guideline Principles.

Abstract

Purpose: Anti-tumor drugs have developed rapidly in recent years. Antibody-drug conjugates (ADCs), as a novel class of targeted biologics, demonstrate significant survival benefits but inevitably cause treatment-related toxicities, with hematologic toxicity-particularly severe neutropenia (grade ≥3)-representing the most prevalent and clinically consequential adverse effect. Currently, no standardized ADC-specific neutropenia management guidelines exist, resulting in fragmented prevention strategies where clinical practice relies on extrapolation from chemotherapy protocols and reactive approaches (e.g., post-onset growth factor support). This study aims to address this gap by proposing a structured preventive framework for ADC-induced neutropenia.

Materials and methods: We conducted a systematic meta-summary of neutropenia data from clinical trials involving ADCs. This evidence was integrated with established principles from chemotherapy-induced neutropenia guidelines and expert consensus. The analysis focused on drug-specific risk profiles, patient-related factors, and evidence-based interventional strategies.

Results: We developed a risk-adapted preventive strategy centered on a "planning for a rainy day" approach. The framework incorporates: (1) risk stratification based on the specific ADC drug and patient factors; (2) primary prophylaxis with long-acting granulocyte colony-stimulating factor (G-CSF) for high-risk patients; (3) secondary prevention strategies for subsequent treatment cycles; and (4) dynamic monitoring of absolute neutrophil counts (ANC) around days 5-7 post-infusion.

Conclusion: Shifting from a reactive to a proactive, personalized prevention paradigm can potentially reduce the incidence of severe neutropenia, subsequent treatment interruptions, and infection-related mortality. This framework provides actionable guidance for standardizing ADC toxicity management and underscores the importance of prioritizing hematologic safety in future ADC development.