Pan-cancer study showed MTM/mL dynamics were more predictive of therapy response than mVAF dynamics, with an observed hazard ratio nearly 2x higher
Natera, Inc., a global leader in cell-free DNA testing, announced a new study published in Molecular Oncology comparing the performance of mean tumor molecules per milliliter (MTM/mL) against mean variant allele frequency (mVAF) for measuring circulating tumor DNA (ctDNA), using Signatera™, Natera’s personalized and tumor-informed molecular residual disease (MRD) test.
To date, mVAF and MTM/mL are the two main metrics that have been used to quantify ctDNA levels in the blood. Unlike mVAF, which is a fraction that can be confounded by changes in total background cfDNA, MTM/mL takes into account total cfDNA as well as plasma volume. The premise is that MTM/mL is therefore more representative of a patient’s true disease burden, a hypothesis that was validated in this study.
The study analyzed ctDNA data generated in 55,183 ctDNA-positive samples from 23,543 patients who underwent testing with Signatera for various cancer diagnoses, and it reported the correlation between MTM/mL and mVAF, as well as the correlations of each with patient outcomes.
Key findings include:
- Among the 18,426 patients with longitudinal ctDNA measurements, 13.3% had discordant ctDNA trajectories (increase/decrease) when calculated using MTM/mL versus mVAF.
- In patients with stage IV disease receiving immunotherapy (N=51), ctDNA dynamics measured in MTM/mL were more predictive of therapy response than those measured in mVAF, with a hazard ratio (HR) nearly 2x higher (MTM/mL HR 16, p<0.0001; mVAF HR 8.8, p<0.0001).
- In a case study of a patient with metastatic triple-negative breast cancer, disease progression during systemic therapy was reflected in increasing MTM/mL values, while mVAF levels remained stable.
“We are pleased to see the publication of these important findings, in which MTM/mL provided a more accurate measure of ctDNA than mVAF, particularly for patients undergoing active therapy which can impact the levels of background cfDNA,” said Minetta Liu, M.D., chief medical officer of oncology at Natera. “Clinicians need tools to enable reliable predictions of therapy response and clinical outcomes. As the only MRD test that uses MTM/mL, this study supports the utility of Signatera for ctDNA quantification, to measure treatment response at critical time points and inform decisions on how patients are managed.”
SOURCE: BusinessWire
