Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell...

Area of Science:

• Oncology
• Hematology
• Biomarkers

Background:

• Diffuse Large B-cell Lymphoma (DLBCL) patients needing immediate therapy are underrepresented in clinical trials.
• Diagnosis-to-treatment interval (DTI) quantifies patient selection bias, with short DTI linked to adverse risk factors and poorer outcomes.

Purpose of the Study:

• To characterize the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes in DLBCL.
• To define objective disease metrics for quantifying selection bias in DLBCL clinical trials.

Main Methods:

• Evaluated pretreatment ctDNA levels in 267 DLBCL patients across multiple centers.
• Correlated ctDNA levels with DTI, total metabolic tumor volumes (TMTVs), International Prognostic Index (IPI), and clinical outcomes.

Main Results:

• Short DTI correlated with advanced stage, higher IPI, and larger TMTV.
• Pretreatment ctDNA levels were associated with stage, IPI, and TMTV, reflecting disease burden.
• Higher ctDNA levels predicted shorter DTI, independent of IPI.
• ctDNA level was prognostic of event-free survival, independent of DTI and IPI.

Conclusions:

• Short DTI reflects baseline tumor burden, objectively measured by pretreatment ctDNA.
• Pretreatment ctDNA levels can quantify and mitigate selection bias in prospective DLBCL clinical trials.