Circulating Tumor DNA Levels Effective for Measuring Disease Burden in Diffuse Large B-Cell Lymphoma

Results of a study found that ctDNA could provide an immediate benefit for mitigating selection bias in DLBCL-centered clinical trials.

Compared with diagnosis-to-treatment intervals (DTIs), circulating tumor DNA (ctDNA) was able to measure disease burden more objectively for patients with diffuse large B-cell lymphoma (DLBCL), according to research published in the Journal of Clinical Oncology.

With these data, ctDNA could provide an immediate benefit in both quantifying and mitigating selection bias associated with DTI for prospective clinical trials examining patients with DLBCL.

“Based on our findings, pretreatment ctDNA levels may be used to both detect and avoid selection biases within clinical trials,” wrote the investigators. “ctDNA is a robust and objective metric using a single assessment blinded to time-based appraisals and can therefore be used to compare average disease burden between study arms and between populations of subjects in different clinical trials.”

The investigative team focused on ctDNA levels for patients with DLBCL who were treated in facilities across Europe and the United States. Median DTI for this cohort of patients was 21 days (range, 0-154 days).

Overall, patients with advanced-stage disease were found to have shorter DTI than patients who had limited-stage disease (median, 18 vs 26 days; P <.001). More, increased International Prognostic Index (IPI) was associated with shorter DTI (P < .001).

The pretreatment ctDNA levels of patients in this study were significantly associated with total metabolic tumor volumes (TMTV), further showing that DTI and ctDNA reflect disease burden. Patients with shorter DTI also had higher pretreatment ctDNA levels (P < .001).

“Both DTI and ctDNA levels were found to be associated with conventional measures of tumor burden such as stage, the International Prognostic Index (IPI), and total metabolic tumor volume,” wrote the investigators. “ctDNA levels predicted short DTI better than the IPI and were independently prognostic of event-free and overall survival in multivariable models also including the IPI and DTI.”

All patients included in the patient population were treated with combination immunochemotherapy in cancer centers across North America and Europe. Pretreatment ctDNA levels were compared with DTI, TMTV, IPI, and outcome.

According to the investigators, a significant limitation of the research is that patients received treatment across several different facilities instead of 1 homogenous cohort treated at a single institution. While this is a limitation, the research team suggests that this reflects the problems that exist with the current different standards across centers for the treatment of DLBCL.

“The subset of patients with DLBCL with aggressive disease in need of immediate therapy is likely under-represented in clinical trials, especially because the urgency of acute clinical presentations may not be compatible with the screening and consent processes required by study protocols. The resulting selection bias can in part be captured by the DTI metric, defined as time between diagnosis and treatment initiation,” wrote the investigators.


Alig S, Macaulay CW, Kurtz DM, et al. Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma. J Clin Oncol. Published April 28, 2021. doi:10.1200/JCO.20.02573