Recent findings presented at the 2025 ASH Annual Meeting and Exposition reveal that circulating tumor DNA (ctDNA) status at the end of treatment (EOT) serves as a more accurate prognostic tool for event-free survival (EFS) outcomes in patients with lymphoma than traditional imaging methods such as PET-CT. The retrospective analysis indicates that patients classified as ctDNA minimal residual disease (MRD) negative experienced significantly better outcomes compared to those who were ctDNA MRD positive.
The study showed that the median EFS was not achieved in the ctDNA MRD-negative group (n = 49), while the median EFS for the ctDNA MRD-positive group (n = 19) was just 1.97 months. The adjusted hazard ratio for the difference between the two groups was a striking 22.43 (95% confidence interval [CI], 6.76-74.45; P < .0001). Furthermore, the 12- and 24-month hazard ratios in the ctDNA MRD-negative population were 0.83 (95% CI, 0.71-0.98) and 0.79 (95% CI, 0.64-0.96), respectively.
Dr. Natalie Galanina, lead study author and clinician investigator at UPMC Hillman Cancer Center in Pittsburgh, highlighted the importance of ctDNA, stating, “EOT ctDNA status can clarify ambiguous imaging results and enables earlier relapse detection.” She emphasized that ctDNA kinetics provide real-time insights into treatment responses and can help predict outcomes for CAR T-cell therapy.
To better understand the utility of ctDNA across various lymphoma subtypes, the research team collected data from patients with newly diagnosed or relapsed/refractory lymphoma across 14 subtypes. The cohort included 1,105 prospectively collected plasma samples from 144 patients. The demographics reflected a broad real-world population, with a median age of 61 years and a predominance of male patients (n = 77; 53%).
Patients in the study had varying stages of lymphoma, with most diagnosed at stage IV (n = 75; 56%). The analysis revealed that pretreatment ctDNA was detectable in an impressive 94% of patients. The median number of tumor molecules per milliliter was approximately 100 in aggressive lymphomas and around 20 in indolent lymphomas.
In comparing ctDNA with PET-CT, the findings were compelling. Patients with a negative PET-CT at EOT (n = 35) showed a median EFS that was not achieved, while those with a positive PET-CT (n = 25) had a median EFS of 5.16 months (adjusted HR, 8.68; 95% CI, 2.41-31.29; P = .0010). Conversely, those with negative ctDNA MRD (n = 44) had a median EFS that was not achieved, compared to 2.04 months for patients with positive ctDNA MRD (n = 16; adjusted HR, 49.77; 95% CI, 9.91-250.02; P < .0001). Galanina remarked on the clinical implications of these results, noting that patients who test PET-positive but ctDNA-negative may not require additional therapy. “Our data show that 75% of PET-positive MRD-negative patients do not progress, indicating they may not need further intervention,” she explained. The study also evaluated ctDNA clearance during frontline therapy, demonstrating its prognostic value across all lymphoma subtypes. Patients who cleared their ctDNA (n = 48) had a median EFS that was not achieved compared to 2.05 months for those who did not clear ctDNA (n = 12; adjusted HR, 8.57; 95% CI, 2.55-28.81; P = .0005).
Dr. Galanina concluded by advocating for the integration of ctDNA testing into routine clinical practice. “MRD assessment supports the incorporation of ctDNA testing into the management and surveillance of lymphoma, allowing for more personalized care,” she said.
These findings underscore the growing potential of ctDNA as a vital tool in the prognosis and treatment of lymphoma, offering hope for improved patient outcomes in the future.
