Liquid Biopsy to Enable Diagnostics and Monitoring for Immune-mediated Lymphoproliferative Disorders

Immune-mediated lymphoproliferative disorders (ILD), as per World Health Organization (WHO HAEM 5) classification, are rare conditions associated with a poor outcome. Current management of ILD is focusing on prevention (e.g.) early detection of ILD with preemptive Epstein Barr virus (EBV) Deoxyribonucleic acid (DNA) levels monitoring, however, this approach is useless for the early detection of EBV-negative ILD. Therapeutic management consists of a reduction in immunosuppressive therapy (RIS), allowing mostly partial and transient responses. Rituximab, an anti-CD20 (cluster differentiation 20) antibody, provides roughly 20-25% of complete and durable responses, thus the majority of ILD patients will require immunochemotherapy, burden with significant toxicity in this challenging population. Implementation of liquid biopsy, also called circulating tumor DNA (ctDNA) in plasma or serum is an area of investigation that is becoming increasingly relevant for clinical practice, allowing for non-invasive monitoring of disease status.

Early detection and monitoring of ILD using ctDNA may allow for preemptive therapy, improved risk-stratification and ultimately, lead to outcome improvement. This multicenter Swiss project will allow a better understanding of ILD mutational landscape and pathogenesis, which could lead to the development of new screening and monitoring approaches for patients suffering from ILD.