Natera, Inc. (NASDAQ: NTRA) announced today that a new study published in the American Journal of Transplantation (AJT) demonstrates significant performance improvements for its Prospera Heart test with Donor Quantity Score (DQS) in detecting allograft rejection in heart transplant patients.
The study evaluated 808 Prospera Heart test samples from 187 heart transplant patients alongside paired endomyocardial biopsies. Researchers compared the performance of Prospera with DQS against the traditional donor-derived cell-free DNA percentage (dd-cfDNA %) method for detecting biopsy-proven allograft rejection.
Superior Performance Metrics
The Prospera Heart test with DQS showed marked improvements across all key performance indicators:
- Sensitivity increased from 78.2% to 86.5%
- Specificity improved from 76.9% to 83.6%
- Area under the curve (AUC) rose from 0.865 to 0.881
- False positive results decreased by 37.3%
These improvements could significantly impact clinical practice by reducing unnecessary biopsies while maintaining high diagnostic accuracy.
Innovative Two-Threshold Approach
Prospera with DQS employs a novel two-threshold algorithm that combines:
- Traditional donor fraction (dd-cfDNA %), which measures donor-derived cell-free DNA as a fraction of total cell-free DNA
- Donor quantity score (DQS), which estimates the total quantity of dd-cfDNA in the blood
This combined approach delivers a single result for risk assessment of both antibody-mediated rejection (AMR) and acute cellular rejection (ACR), the two primary forms of transplant rejection.
"This publication provides evidence that combining dd-cfDNA % with DQS improves the accuracy of dd-cfDNA testing for acute rejection over dd-cfDNA %-alone," said Josef Stehlik, M.D., M.P.H., one of the study investigators and medical director of the Heart Transplant Program and co-chief of the Advanced Heart Failure Program at the University of Utah.
Dr. Stehlik added, "It is encouraging to see that this novel approach significantly reduced false positive results and will help to obviate unnecessary biopsies in clinical care. This is another step in providing enhanced care for heart transplant patients using noninvasive tools to determine risk of rejection."
Growing Evidence Base
The AJT publication adds to a growing body of evidence supporting the use of DQS in solid organ transplant monitoring. Previous research has demonstrated the value of this approach in kidney transplantation, as shown in a study by Halloran et al. Additionally, Natera has presented supporting data in its 2022 DEDUCE study and recently announced findings from the DEFINE-HT study.
"Ongoing datasets continue to demonstrate the robust performance of Prospera Heart with DQS, indicating its potential to reduce reliance on endomyocardial biopsies – procedures that carry inherent risk and cause patient discomfort," noted Michael Olympios, M.D., Medical Director of Heart Transplant at Natera.
Clinical Implications for Transplant Patients
Heart transplant recipients currently undergo routine endomyocardial biopsies to monitor for rejection, an invasive procedure that carries risks including bleeding, infection, and arrhythmias. A highly accurate non-invasive alternative could significantly improve patient experience and potentially reduce healthcare costs.
The Prospera test works by measuring the fraction of donor-derived cell-free DNA in the recipient's blood without requiring prior donor or recipient genotyping. This allows physicians to evaluate the need for diagnostic testing or interpret the results of an invasive biopsy when considering the diagnosis of active rejection.
Natera's technology leverages single-nucleotide polymorphism-based massively multiplexed PCR (mmPCR) technology to identify allograft rejection non-invasively with high precision and accuracy. The test has been clinically and analytically validated for performance regardless of donor relatedness, rejection type, and clinical presentation.
Future Research Directions
Natera continues to advance research in this field with the randomized ACES trial currently in progress. This ongoing research aims to further refine diagnostic approaches and improve clinical outcomes for heart transplant recipients.
As non-invasive monitoring tools continue to evolve, transplant medicine moves closer to more personalized care protocols that may reduce the burden of invasive procedures while maintaining or improving the accuracy of rejection detection.
