Natera, Inc. (NASDAQ:NTRA), a global leader in cell-free DNA and precision medicine, today announced the publication of new data in Blood Neoplasia, validating the prognostic and predictive value of Signatera in patients with both newly diagnosed and relapsed/refractory (R/R) lymphoma.

PET/CT scans serve as the standard tool for assessing treatment response in lymphoma, but their performance is limited, with positive predictive value (PPV) reported as low as 50% and negative predictive value (NPV) as low as 80%.1-3 To address this unmet need, the National Comprehensive Cancer Network® (NCCN®) guidelines were recently updated to include circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) assessment as a confirmatory method for positive PET/CT scans.

The prospective, real-world study conducted by Galanina et al. evaluated a representative cohort of 144 newly diagnosed or R/R patients across 14 distinct indolent and aggressive lymphoma subtypes, with analysis of 1,105 plasma samples collected at baseline, during therapy, at the end of therapy (EOT), and throughout surveillance. Signatera status was compared to standard-of-care imaging and clinical outcomes to evaluate its predictive and prognostic utility in real-world disease management. Key findings include:

  • Superior prognostic ability over PET/CT:
    • EOT Signatera-positivity was prognostic of significantly inferior event-free survival (EFS) (adj HR: 45.33; p<0.0001) and was the strongest independent predictor of EFS in a multivariate analysis (HR: 80.83 vs. PET/CT HR: 5.18; p<0.001).
    • Signatera demonstrated superior PPV vs. PET/CT at EOT (100% vs. 62%; p<0.0001). Among discordant ctDNA/PET cases, the Signatera test result was confirmed as correct in 85% of instances.
    • During surveillance, Signatera-positivity was strongly prognostic (HR: 33.74; p<0.0001), demonstrating a sensitivity of 91% and specificity of 92%.
  • Predictive of response across the treatment continuum:
    • Signatera clearance during 1L therapy was associated with significantly improved EFS (adj HR: 8.57; p=0.0005).
    • For R/R patients post CAR-T therapy, Signatera clearance was associated with durable remission, while Signatera-positive patients experienced disease progression or death, and a median durable treatment interval of 16.1 vs. 1.97 months, respectively (p=0.0091).