The AlloMap™ genomic biomarker story: 10 years after

Abstract

Over the last >20 years, we have co-developed the rationale for the first diagnostic and prognostic leukocyte gene expression profiling (GEP) biomarker test in transplantation medicine that gained US-FDA-regulatory clearance and international evidence-based medicine guideline acceptance to rule out moderate/severe acute cellular cardiac allograft rejection without invasive endomyocardial biopsies (EMB). Based on this test, a non-invasive clinical algorithm was implemented since 2005. After clinical implementation, this GEP-based monitoring in direct comparison with an EMB-based strategy was non-inferior with respect to detection of clinical rejection, defined as new onset allograft dysfunction with/without histology of ACR, re-transplantation or death, and at the same time improved patient satisfaction. Subsequently, we demonstrated the test's capacity when used as serial monitoring tool to predict these clinical rejection events. In this Personal Viewpoint article, I will discuss the various decision-making branching points that were made in the AlloMap biomarker test development to inform future genomic biomarker test development projects.

Differences in Gene Expression in Older Compared With Younger Kidney Transplant Recipients

“…This approach has been applied successfully for the prediction of allograft rejection in heart transplant recipients. 3,4…”

MicroRNAs: Key Regulators to Understand Osteoclast Differentiation?

“…Moreover, these kinds of tests are likely best suited to a companion role. In contrast to RNA or DNA-based tests, especially that indicate the presence of SNP or a specific expression profile (98), miRNA tests produce results that are more difficult to interpret. While many miRNAs were reported as biomarkers in many reports (99), most miRNAs are expressed widely in a non-cell-specific manner, and their levels of expression are not differing drastically between patients' group and controls.…”

A Peripheral Blood Transcriptome Biomarker Test to Diagnose Functional Recovery Potential in Advanced Heart Failure

“…After completion of this clinical validity study of developing the test in a framework of diagnosing the potential of future organ function recovery and frailty reversal, FDA clearance and clinical implementation, we plan to conduct a clinical utility trial, testing the impact of adding the test information to the best current clinical prediction tools of net health outcomes as we did with the AlloMAP™ test development [137,138]. We plan to make this test commercially available, likely using the Nanostring platform that has already been used for an FDA-cleared In vitro-Diagnostic Multivariate Index Assay test.…”