Information Regarding Noridian and MolDX’s Contractor Advisory Committee Meetings on Molecular Diagnostic Testing for Organ Rejection

On November 16 and November 17, 2022, Noridian Healthcare Solutions and MolDX held Contractor Advisory Committee (CAC) meetings, during which a panel of subject matter experts were asked to review the clinical evidence for molecular diagnostic testing for acute rejection in kidney, liver, lung, and heart transplant.

In anticipation of the meetings, Noridian released a list of key questions to be addressed during the meetings and a survey of publications regarding the clinical evidence for these tests.

CareDx has submitted responses to these questions to Noridian and MolDX. Copies of CareDx’s responses are below. These responses are intended to address the specific questions posed by Noridian and MolDX and do not constitute medical advice. Any CareDx testing should be ordered, and any diagnosis and treatment should be based on, the independent judgment of the treating clinician.

In addition, below please find: (1) one-page summaries on CareDx’s kidney, heart, and lung tests; (2) lists of key publications for CareDx’s kidney, heart, and lung tests; and (3) comprehensive publication lists for AlloSure Kidney and CareDx’s heart testing.

Summaries of CareDx Testing
One Page Summary on CareDx Kidney Testing
One Page Summary on CareDx Heart Testing
One Page Summary on CareDx Lung Testing

CareDx’s Responses to CAC Questions
CareDx’s Responses to Questions Regarding AlloSure Kidney
CareDx’s Responses to Questions Regarding AlloMap Kidney
CareDx’s Responses to Questions Regarding AlloSure Heart and AlloMap Heart
CareDx’s Responses to Questions Regarding AlloSure Lung

Key Publications in Kidney

Dandamudi et al. Longitudinal Evaluation of Donor-Derived Cell free DNA in Pediatric Kidney Transplantation.  Clin J Am Soc Nephrol. 2022 Nov;17(11):1646-1655.

Obrisca et al. Combining donor-derived cell-free DNA and donor specific antibody testing as non-invasive biomarkers for rejection in kidney transplantation.  Scientific Reports. 2022 Sep 5;12(1):15061.

Gupta et al. Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies. Transplantation. 2022 May 1;106(5):1061-1070.

Cheung et al. Validation of a gene expression signature to measure immune quiescence in kidney transplant recipients in the CLIA setting. Biomark Med. 2022 Jun;16(8):647-661.

Bu et al. Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study.  Kidney Int. 2021 Dec 22;S0085-2538(21)01168-6

Akalin et al. Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation. Kidney360. 2021 Sep 28;2(12):1998-2009

Sawinski et al. Association between dd-cfDNA levels, de novo donor specific antibodies, and eGFR decline: An analysis of the DART cohort.  Clinical Transplantation. 2021;35:e14402.

Melancon et al. Donor-Derived Cell Free DNA: Is It All the Same?  Kidney360. 2020 Jun 19;1(10):1118-1123.

Kant et al. Donor-derived Cell-free DNA and the Prediction of BK Virus-associated Nephropathy. Transplant Direct. 2020 Oct 23;6(11):e622.

Stites et al. High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury. Am J Transplant. 2020;00:1-8. PMID 32056331.

Sureshkumar et al. Impact of Kidney Transplant Type and Previous Transplant on Baseline Donor-Derived Cell Free DNA. Transpl Int. 2020 Jun 11. doi: 10. 1111/tri.13673.

Puliyanda et al. Donor-Derived Cell Free DNA (dd-cfDNA) for Detection of Allograft Rejection in Pediatric Kidney Transplants. Pediatr Transplant. 2020 Nov 20;e13850.

Huang et al. Donor-derived cell-free DNA combined with histology improves prediction of estimated glomerular filtration rate over time in kidney transplant recipients compared with histology alone. Transplantation direct. 2020 Aug;6(8).

Mehta et al. Repeat kidney transplant recipients with active rejection have elevated donor-derived cell0-free DNA.  Am J Transplant. 2019;19:1597–1598.

Jordan et al. Donor-derived cell-free DNA identifies antibody-mediated rejection in donor specific antibody positive kidney transplant recipients. Transplant Direct. 2018;4:e379.

Bromberg et al. Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications.  J Appl Lab Med. 2017 Nov 1;2(3):309-321.

Bloom et al. Cell-free DNA and active rejection in kidney allografts. J Am Soc Nephrol. 2017;28:2221-2232. PMID 28280140.

Grskovic et al. Validation of a clinical-grade assay to measure donor-derived cell-free DNA in solid organ transplant recipients. J Mol Diag. 2016 Nov 1;18(6):890-902.

Key Publications in Heart

Alam et al. Evolving the surveillance and workup of heart transplant rejection: A real-world analysis of the Molecular Microscope Diagnostic System. Am J Transplant. May 05 2022; doi:10.1111/ajt.17087

Kamath et al. Variability in Donor-Derived Cell-Free DNA Scores to Predict Mortality in Heart Transplant Recipients – A Proof-of-Concept Study. Front Immunol. 2022;13:825108.

Amadio et al. Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19. CJC Open. May 2022;4(5):479-487.

Henricksen et al. Combining donor derived cell free DNA and gene expression profiling for non-invasive surveillance after heart transplantation. Clin Transplant. May 12 2022:e14699.

Feingold et al. Early findings after integration of donor-derived cell-free DNA into clinical care following pediatric heart transplantation. Pediatr Transplant. Feb 2022;26(1):e14124.

Gondi et al. Single-Center Utilization of Donor-Derived Cell-Free DNA Testing in the Management of Heart Transplant Patients. Clin Transplant. 2021 Feb 19;e14258.

Holzhauser et al. Donor derived cell free DNA is Associated with Cardiac Allograft Vasculopathy. Clin Transplant. 2020 Dec 25;e14206.

Chih et al. Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement on Heart Transplantation: Patient Eligibility, Selection, and Post-Transplantation Care, Canadian Journal of Cardiology, Volume 36, Issue 3, 2020, p. 335-356.

Khush et al. Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study. Am J Transplant. 2019;19:2889–2899.

Moayedi et al. Gene expression profiling and racial disparities in outcomes after heart transplantation. The Journal of Heart and Lung Transplantation. 2019 Aug 1;38(8):820-9.

Grskovic et al. Validation of a clinical-grade assay to measure donor-derived cell-free DNA in solid organ transplant recipients. J Mol Diag. 2016 Nov 1;18(6):890-902.

Crespo-Leiro et al. Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II. European Heart Journal. 2016 Sep 1;37(33):2591-601.

Crespo-Leiro et al. Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients. BMC cardiovascular disorders. 2015 Dec;15(1):1-9.

Kobashigawa et al. Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: early invasive monitoring attenuation through gene expression trial. Circulation: Heart Failure. 2015 May;8(3):557-64.

Deng et al. Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients. Transplantation. 2014 Mar 3;97(6):708.

Costanzo et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. The Journal of heart and lung transplantation. 2010 Aug 1;29(8):914-56.

Pham et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. New England Journal of Medicine. 2010 May 20;362(20):1890-900.

Deng et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. American Journal of Transplantation. 2006 Jan;6(1):150-60.

Key Lung Publications

Keller et al. Donor-derived cell-free DNA as a composite marker of acute lung allograft dysfunction in clinical care.  J Heart Lung Transplant. 2022 doi 10.1016/j.healun.2021.12.009

Keller et al. Biological Variation of Donor-Derived Cell-Free DNA in Stable Lung Transplant Recipients.  J Appl Lab Med. 2022 Jan 12;jfab171.

Khush et al. Donor-derived Cell-free DNA Levels by Next Generation Targeted Sequencing are Elevated in Allograft Rejection after Lung Transplantation.  ERJ Open Res. 2021; 7:00462-2020

Sayah et al. Plasma Donor-derived Cell-free DNA Levels Are Increased During Acute Cellular Rejection After Lung Transplant: Pilot Data.  Transplant Direct. 2020 Sep 24;6(10):e608.

Comprehensive Publication Lists