ctDNA Better Predicts Lymphoma Outcomes Than PET-CT, Study Shows

Research presented at the 2025 ASH Annual Meeting and Exposition indicates that measuring circulating tumor DNA (ctDNA) at the end of treatment (EOT) provides a more accurate prediction of event-free survival (EFS) outcomes for lymphoma patients than conventional imaging methods such as PET-CT. The findings reveal significant disparities in EFS based on ctDNA status, underscoring the potential for ctDNA to enhance patient management.

In the study, patients who tested negative for minimal residual disease (MRD) through ctDNA demonstrated a median EFS that was not achieved (NA), while those with ctDNA-MRD positivity had a median EFS of just 1.97 months. The analysis included 49 patients in the ctDNA-MRD-negative group and 19 in the ctDNA-MRD-positive group, yielding an adjusted hazard ratio of 22.43 (95% CI, 6.76-74.45; P < .0001).

Study Insights and Patient Demographics

Lead study author Natalie Galanina, MD, a clinician investigator at UPMC Hillman Cancer Center in Pittsburgh, Pennsylvania, emphasized the significance of ctDNA in providing clarity amidst ambiguous imaging results. “EOT ctDNA status can clarify ambiguous imaging results and enables earlier relapse detection,” she stated during her presentation. Galanina also noted that ctDNA kinetics offer insights into treatment responses during first-line therapy and can predict responses to CAR T-cell treatment.

The research utilized a large cohort of 144 patients with newly diagnosed and relapsed/refractory lymphoma, spanning 14 subtypes. The median age of participants was 61 years, with the majority being male (53%). Most patients presented with advanced-stage disease, including 56% at stage IV.

The study collected 1,105 plasma samples for ctDNA assessment, incorporating diverse lymphoma types, including aggressive T-cell and B-cell lymphomas, and indolent forms such as follicular and marginal zone lymphoma. This comprehensive approach aimed to bridge the knowledge gap regarding ctDNA’s prognostic capabilities across various lymphoma subtypes.

ctDNA vs. Traditional Imaging Methods

Additional findings suggest that ctDNA is a more reliable indicator of treatment response than traditional imaging tools. For instance, patients with a negative PET-CT at EOT exhibited a median EFS that was NA, while those with positive PET-CT had a median EFS of 5.16 months. In contrast, ctDNA-MRD-negative patients experienced a median EFS of NA compared to 2.04 months for ctDNA-MRD-positive patients.

The data revealed that even in cases where PET-CT results were negative, the presence of ctDNA-MRD could indicate a risk of relapse. Galanina highlighted that approximately 75% of PET-positive MRD-negative patients did not progress, suggesting they may not require additional therapy. This insight supports the integration of ctDNA testing into routine assessments to better stratify patient risk for relapse.

The research also explored ctDNA clearance during frontline therapy, which proved to be prognostic across all lymphoma subtypes. Patients who cleared their ctDNA during treatment had a median EFS that was NA, while those who did not achieve clearance had a median EFS of 2.05 months.

Galanina explained that early ctDNA clearance, particularly by the first cycle of treatment, could inform potential therapy de-escalation, especially for older patients or those with comorbidities. Furthermore, the predictive value of ctDNA clearance was maintained even in patients undergoing CAR T-cell therapy, where most MRD-positive patients who cleared ctDNA within three months achieved durable remission at one year.

In conclusion, the study supports the integration of ctDNA assessment into clinical practice for lymphoma management. Galanina stated, “MRD assessment supports the integration of ctDNA testing into routine clinical management and surveillance to personalize lymphoma care.” The findings highlight the need for ongoing research to optimize ctDNA use in monitoring and treatment strategies for lymphoma patients.