Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma: from Bench to Bedside?

Area of Science:

• Oncology
• Molecular Diagnostics
• Hematologic Malignancies

Background:

• Diffuse large B-cell lymphoma (DLBCL) treatment is often standardized due to insufficient characterization of disease heterogeneity.
• Current diagnostic tools have limitations in fully understanding DLBCL's complex clinical and molecular features.
• Personalized medicine approaches are needed to improve variable outcomes in DLBCL patients.

Purpose of the Study:

• To review the potential of circulating tumor DNA (ctDNA) sequencing for personalizing DLBCL care.
• To explore the utility of ctDNA assays in various DLBCL treatment settings.
• To advocate for the integration of ctDNA into clinical trials and practice for DLBCL.

Main Methods:

• Review of current literature on ctDNA assays and their application in DLBCL.
• Discussion of ctDNA's role in risk stratification, molecular response assessment, and minimal residual disease (MRD) monitoring.
• Exploration of potential clinical trial designs incorporating ctDNA biomarkers.

Main Results:

• ctDNA sequencing is a developing technology with significant potential for DLBCL management.
• Evidence supports ctDNA's utility for estimating tumor burden, liquid genotyping, and assessing treatment response.
• ctDNA can monitor for MRD, identify resistance, and predict relapse in DLBCL patients.

Conclusions:

• ctDNA sequencing offers a promising avenue for personalized DLBCL treatment strategies.
• Integrating ctDNA into clinical trials is crucial for patient selection and response-adapted designs.
• Liquid biopsy using ctDNA may guide clinical decisions, especially when imaging is equivocal or during severe toxicities.