Signatera assay ctDNA testing showed stronger prognostic and predictive value than PET/CT imaging across lymphomas.
Tumor-informed circulating tumor DNA (ctDNA) testing with the Signatera assay demonstrated stronger prognostic and predictive value compared with standard PET/CT imaging in patients with newly diagnosed or relapsed/refractory lymphomas, according to findings from a prospective, real-world cohort study published in Blood Neoplasia.1
For patients with ctDNA testing results available at end of treatment (EOT; n = 68), EOT ctDNA–molecular residual disease (MRD) positivity was prognostic of significantly inferior event-free survival (EFS; adjusted HR [aHR], 28.03; 95% CI, 8.16-96.29; P < .0001). In a multivariate analysis incorporating both ctDNA and PET/CT status, ctDNA-MRD positivity was the strongest independent predictor of inferior EFS (HR, 80.83; 95% CI, 12.07-541.3; P < .001).
Among patients with both EOT ctDNA MRD and EOT PET/CT results available (n = 59), ctDNA-MRD positivity conferred a 100% positive predictive value (PPV) for inferior EFS compared with 62% for PET/CT positivity (P < .0001). During posttreatment surveillance, ctDNA-MRD positivity remained strongly prognostic of inferior EFS (aHR, 33.74; 95% CI, 9.34-121.82; P < .0001), with a sensitivity of 91%, specificity of 92%, PPV of 87%, and negative predictive value (NPV) of 95%. Moreover, EOT ctDNA-MRD positivity demonstrated a risk of inferior EFS that was significantly higher than ctDNA-MRD negativity (aHR, 45.33; 95% CI, 10.19-201.65; P <.0001).
“Signatera delivers consistent and reliable insights across multiple lymphoma subtypes,” study author Natalie Galanina, MD, stated in a news release.2 “ctDNA/MRD assessment is transforming how we evaluate treatment response, offering the opportunity to move beyond conventional imaging and toward more precise, individualized, and dynamic treatment decisions.”
Galanina is an associate professor of medicine at the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania.
The study evaluated 144 real-world patients with newly diagnosed or relapsed/refractory lymphoma across indolent and aggressive subtypes, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, follicular lymphoma, and peripheral T-cell lymphoma.1
To be included in ctDNA analysis, patients needed to have both complete clinical annotation and demonstrate the absence of concomitant malignancies.
Patients underwent ctDNA testing at baseline, during therapy, at EOT, and throughout posttreatment surveillance, and Signatera status was compared with standard-of-care imaging and clinical outcomes.
The primary outcome of the analysis was EFS, which was defined as time from the start of therapy without progression, death, or salvage treatment.
Characteristics of the overall population (n = 144) revealed that patients had a median age of 61 years (range, 18-84) and were mostly male (53%). Most patients had stage IV disease (56%) and an ECOG performance status of 0 (46%). Revised International Prognostic Index scores were very good (25.2%) or poor (26.8%), with 80 patients having scores that were not reported. Common first-line therapies in the overall population were R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone; 49%), other (22%), and other rituximab-containing regimens (12%).
Significantly inferior EFS was also shown for patients who were EOT ctDNA-MRD positive with aggressive lymphoma (n = 18; aHR, 25.29; 95% CI, 7.35-86.99; P < .0001) and DLBCL (n = 10; aHR, 16.58; 95% CI, 3.64-75.48; P = .0003)
Among patients who were ctDNA-MRD positive at baseline but achieved ctDNA-MRD clearance during first-line therapy (n = 48) also demonstrated significant EFS improvements (aHR, 8.57; 95% CI, 2.55-28.81; P = .005). For those who achieved a complete response and later relapsed (n = 6), ctDNA-MRD testing identified molecular recurrence a median of 5.3 months (range, 0.7-7.1) before imaging- or biopsy-confirmed relapse.
Among patients with relapsed/refractory lymphoma who had both pre- and post–chimeric antigen receptor (CAR) T-cell therapy ctDNA data (n =12), those who achieved ctDNA-MRD negativity after CAR T-cell therapy had a median relapse-free interval of 16.1 months, compared with 1.97 months among those who remained ctDNA-MRD positive (P = .0091). All 3 patients who were ctDNA-MRD negative before CAR T-cell infusion remained relapse-free after therapy.
Overall agreement between ctDNA-MRD results and clinically adjudicated outcomes was 96.8%, and among cases where ctDNA and PET/CT results diverged, the ctDNA-MRD result was corroborated by clinical outcome in 85% of instances.
“The ability to reliably detect and monitor MRD over time has the potential to impact the approach to treatment of lymphoma,” Minetta Liu, MD, chief medical officer of oncology and early cancer Detection at Natera, added in a news release.2 “By enabling visibility into recurrence earlier than imaging, Signatera testing creates a window for more timely, risk-adapted interventions that could meaningfully change patient management.”
