Real-world data suggests that circulating tumor DNA (ctDNA) status more accurately captures event-free survival (EFS) outcomes than Positron Emission Tomography-Computed Tomography (PET-CT). ctDNA at the end of treatment strongly predicts outcomes across various lymphoma subtypes, outperforming imaging techniques and supporting its role in personalized disease monitoring.
The study, presented at the 2025 ASH Annual Meeting and Exposition, analyzed real-world data from 144 patients with lymphoma. It found that the presence of ctDNA at the end of treatment (EOT) was a strong prognostic indicator, with MRD negativity linked to significantly longer EFS across lymphoma subtypes. The median EFS was not achieved in the ctDNA-MRD-negative group, compared to 1.97 months in the ctDNA-MRD-positive group, with an adjusted HR of 22.43.
The study also revealed that early or delayed ctDNA clearance was associated with improved EFS outcomes, supporting ctDNA's role in routine management and surveillance. Additionally, ctDNA provided a better indication of treatment response than traditional imaging, with patients who had negative ctDNA-MRD at EOT experiencing a median EFS of 2.04 months, compared to 5.16 months in those with positive ctDNA-MRD.
Furthermore, ctDNA was the most significant predictor of EFS after correcting for other factors, including age, tumor histology, and stage. Early ctDNA clearance during frontline therapy was also prognostic of outcomes in all lymphoma subtypes, with a median EFS of 2.05 months in patients who cleared their ctDNA, compared to 2.05 months in those who did not.
The study also explored the predictive value of ctDNA in CAR T-cell therapy, suggesting that ctDNA clearance retains its predictive value in this setting as well. Most MRD-positive patients who cleared ctDNA within 3 months post-CAR T attained durable remission at 1 year.
In conclusion, the study highlights the potential of ctDNA as a valuable prognostic and predictive biomarker in lymphoma, supporting its integration into routine clinical management and surveillance to personalize lymphoma care.
