POSITIVE ENVISIA GENOMIC CLASSIFIER RESULT PREDICTS CLINICAL PROGRESSION IN FIBROTIC INTERSTITIAL LUNG DISEASE

Abstract

SESSION TITLE: Late Breaking Diffuse Lung Disease PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: Progressive deterioration is the clinical hallmark of Usual Interstitial Pneumonia (UIP). While this entity is an essential criterion for ascertaining a diagnosis of Idiopathic Pulmonary Fibrosis (IPF), it is nonspecific, and it is associated with poor prognosis in patients with Progressive Pulmonary Fibrosis (PPF) beyond IPF. An accurate UIP diagnosis in both groups guides treatment choices. The Envisia Genomic Classifier (EGC) is a clinically validated molecular diagnostic test that identifies a genomic UIP pattern in transbronchial biopsies. Given that a UIP genomic signature reflects the molecular biology of the underlying interstitial lung disease (ILD), we hypothesized that an EGC (+) result is a biomarker of disease progression in patients with fibrotic interstitial ling diseases (ILD).METHODS: We identified 135 patients enrolled in the BRAVE study who underwent pathological evaluation for an undiagnosed ILD, had an EGC result, and had longitudinal forced vital capacity (FVC) measurements. Patients were required to have an FVC performed within six months of BRAVE enrollment and additional measurements at least six months after the baseline FVC. Retrospective analyses of EGC result, change in FVC, and treatment for ILD were performed.RESULTS: Of the 135 patients evaluated, 73 (54%) patients had an EGC UIP (+) result. Overall, patients with an EGC UIP (+) result had a baseline FVC of 66.9% predicted with an absolute 1-year decline in FVC of 3.7% compared to 62 (46%) patients with an EGC UIP negative (-) result who had a baseline FVC of 73.4% with an absolute 1-year decrease in FVC of 0.1% (p=0.06). The 1-year decline in FVC in the Envisia UIP (+) group was observed irrespective of findings on pathology. In pathology UIP (+) patients, 1-yr decline in FVC was 2.4%, compared to a decline of 1.8% in patient in whom pathology was diagnostic but negative for UIP and 1.4% in patients in whom pathology was nondiagnostic (p=0.9).CONCLUSIONS: An Envisia Genomic Classifier UIP (+) result identified patients who demonstrated disease progression as measured by a decline in FVC in the subsequent 6 + months. FVC decline was observed even in ECG UIP (+) patients in whom pathology was negative for UIP and those in whom pathology was considered nondiagnostic.CLINICAL IMPLICATIONS: It has been established previously that an EGC UIP (+) result has clinical utility in multidisciplinary discussions for making a confident diagnosis of ILD including IPF in the appropriate clinical setting. These results suggest the additional clinical utility of an EGC UIP (+) result as a biomarker for predicting PPF and may prompt consideration of early antifibrotic therapy with the potential for improved outcomes in patients with ILD. Further studies are warranted to determine utility and validate results from this study.DISCLOSURES:Employee relationship with Veracyte Please note: 2/1/2021-present by William Bulman, value=SalaryEmployee relationship with Veracyte Inc. Please note: 05/19/2019 - present Added 06/06/2022 by Jeremy Burbanks-Ivey, value=SalaryEmployee relationship with Veracyte Please note: >$100000 by Jing Huang, value=SalaryEmployee relationship with Veracyte Please note: >$100000 by Marla Johnson, value=SalaryEmployee relationship with Veracyte, Inc. Please note: 2008-present by Giulia Kennedy, value=SalarySpeaker/Speaker's Bureau relationship with Genentech Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=HonorariaSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=HonorariaResearch relationship with Celgene Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Novartis Please note: pending Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Bellerophon Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Galactic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportResearch relationship with Respivant Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportMy spouse/partner as a Employee relationship with Medtronic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=SalaryConsultant relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with Bellerophon Please note: active Added 03/28/2022 by Lisa Lancaster, value=HonorariaConsultant relationship with BMS Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeGrant/Research support relationship with fibrogen Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportGrant/Research support relationship with Pliant Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportConsultant relationship with Astrazeneca Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with nashville biosciences Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with DevProBiopharma Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeResearch Grant relationship with Roche Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research SupportConsultant relationship with Daewoong Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeConsultant relationship with United Therapeutics Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting feeEmployee relationship with Veracyte Please note: 4.5 years Added 03/31/2022 by Lori Lofaro, value=SalaryRemoved 06/08/2022 by Lori LofaroEmployee relationship with Veracyte Please note: 5 years Added 06/08/2022 by Lori Lofaro, value=SalaryEmployee relationship with Veracyte, Inc. Please note: 07/2018 - Present Added 03/31/2022 by Eric Morrie, value=SalaryScientific Medical Advisor relationship with Veracyte Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting feeResearch grant reviewer relationship with Boerhinger Ingelheim Please note: 2020-2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting feeScientific Medical Advisor relationship with United therapeutics Please note: 2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting feeScientific Medical Advisor relationship with BMS Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting feeScientific Medical Advisor relationship with roche -genentech Please note: 2020++ Added 06/11/2022 by Ganesh Raghu, value=nonesceintific medical advisor relationship with Fibrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneRemoved 06/11/2022 by Ganesh RaghuScientific Medical Advisor relationship with FIbrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneScientific Medical Advisor relationship with ROCHE -GENENTECH Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneScientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONRRemoved 06/11/2022 by Ganesh RaghuScientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONEScientific Medical Advisor relationship with BELLEROPHAN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONEDATA SAFETY MONITORIN BOARD relationship with AVALYN Please note: 2019 - Added 06/11/2022 by Ganesh Raghu, value=noneRemoved 06/11/2022 by Ganesh RaghuScientific Medical Advisor relationship with AVALYN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=noneGrant relationship with Boehringer Ingelheim Please note: 2014 to present by Christopher Ryerson, value=Grant/ResearchConsultant relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=Consulting feeSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=RoyaltyConsultant relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=Consulting feeSpeaker/Speaker's Bureau relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=RoyaltySpeaker/Speaker's Bureau relationship with Cipla Ltd. Please note: 2020 by Christopher Ryerson, value=RoyaltyAdvisory Committee Member relationship with Veracyte Please note: 2021 by Christopher Ryerson, value=Consulting feeAdvisory Committee Member relationship with Astra Zeneca Please note: 2021 by Christopher Ryerson, value=Consulting feeConsultant relationship with Pliant Therapeutics Please note: ongoing Added 06/06/2022 by Christopher Ryerson, value=Consulting feeAdvisory Committee Member relationship with veracyte Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting feeAdvisory Committee Member relationship with genentech Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting feeAdvisory Committee Member relationship with united therapeutics Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting feeSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=HonorariaAdvisory Committee Member relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeSpeaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeAdvisory Committee Member relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeSpeaker/Speaker's Bureau relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting feeAdvisory Committee Member relationship with Veracyte Please note: May 2022 Added 06/21/2022 by Athol Wells, value=Consulting fee SESSION TITLE: Late Breaking Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Progressive deterioration is the clinical hallmark of Usual Interstitial Pneumonia (UIP). While this entity is an essential criterion for ascertaining a diagnosis of Idiopathic Pulmonary Fibrosis (IPF), it is nonspecific, and it is associated with poor prognosis in patients with Progressive Pulmonary Fibrosis (PPF) beyond IPF. An accurate UIP diagnosis in both groups guides treatment choices. The Envisia Genomic Classifier (EGC) is a clinically validated molecular diagnostic test that identifies a genomic UIP pattern in transbronchial biopsies. Given that a UIP genomic signature reflects the molecular biology of the underlying interstitial lung disease (ILD), we hypothesized that an EGC (+) result is a biomarker of disease progression in patients with fibrotic interstitial ling diseases (ILD). METHODS: We identified 135 patients enrolled in the BRAVE study who underwent pathological evaluation for an undiagnosed ILD, had an EGC result, and had longitudinal forced vital capacity (FVC) measurements. Patients were required to have an FVC performed within six months of BRAVE enrollment and additional measurements at least six months after the baseline FVC. Retrospective analyses of EGC result, change in FVC, and treatment for ILD were performed. RESULTS: Of the 135 patients evaluated, 73 (54%) patients had an EGC UIP (+) result. Overall, patients with an EGC UIP (+) result had a baseline FVC of 66.9% predicted with an absolute 1-year decline in FVC of 3.7% compared to 62 (46%) patients with an EGC UIP negative (-) result who had a baseline FVC of 73.4% with an absolute 1-year decrease in FVC of 0.1% (p=0.06). The 1-year decline in FVC in the Envisia UIP (+) group was observed irrespective of findings on pathology. In pathology UIP (+) patients, 1-yr decline in FVC was 2.4%, compared to a decline of 1.8% in patient in whom pathology was diagnostic but negative for UIP and 1.4% in patients in whom pathology was nondiagnostic (p=0.9). CONCLUSIONS: An Envisia Genomic Classifier UIP (+) result identified patients who demonstrated disease progression as measured by a decline in FVC in the subsequent 6 + months. FVC decline was observed even in ECG UIP (+) patients in whom pathology was negative for UIP and those in whom pathology was considered nondiagnostic. CLINICAL IMPLICATIONS: It has been established previously that an EGC UIP (+) result has clinical utility in multidisciplinary discussions for making a confident diagnosis of ILD including IPF in the appropriate clinical setting. These results suggest the additional clinical utility of an EGC UIP (+) result as a biomarker for predicting PPF and may prompt consideration of early antifibrotic therapy with the potential for improved outcomes in patients with ILD. Further studies are warranted to determine utility and validate results from this study. DISCLOSURES: Employee relationship with Veracyte Please note: 2/1/2021-present by William Bulman, value=Salary Employee relationship with Veracyte Inc. Please note: 05/19/2019 - present Added 06/06/2022 by Jeremy Burbanks-Ivey, value=Salary Employee relationship with Veracyte Please note: >$100000 by Jing Huang, value=Salary Employee relationship with Veracyte Please note: >$100000 by Marla Johnson, value=Salary Employee relationship with Veracyte, Inc. Please note: 2008-present by Giulia Kennedy, value=Salary Speaker/Speaker's Bureau relationship with Genentech Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Honoraria Research relationship with Celgene Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Novartis Please note: pending Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Bellerophon Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Galactic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Research relationship with Respivant Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support My spouse/partner as a Employee relationship with Medtronic Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Salary Consultant relationship with Galapagos Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with Bellerophon Please note: active Added 03/28/2022 by Lisa Lancaster, value=Honoraria Consultant relationship with BMS Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Grant/Research support relationship with fibrogen Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Grant/Research support relationship with Pliant Please note: active Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Consultant relationship with Astrazeneca Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with nashville biosciences Please note: remote Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with DevProBiopharma Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Research Grant relationship with Roche Please note: ongoing Added 03/28/2022 by Lisa Lancaster, value=Grant/Research Support Consultant relationship with Daewoong Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Consultant relationship with United Therapeutics Please note: active Added 03/28/2022 by Lisa Lancaster, value=Consulting fee Employee relationship with Veracyte Please note: 4.5 years Added 03/31/2022 by Lori Lofaro, value=Salary Removed 06/08/2022 by Lori Lofaro Employee relationship with Veracyte Please note: 5 years Added 06/08/2022 by Lori Lofaro, value=Salary Employee relationship with Veracyte, Inc. Please note: 07/2018 - Present Added 03/31/2022 by Eric Morrie, value=Salary Scientific Medical Advisor relationship with Veracyte Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Research grant reviewer relationship with Boerhinger Ingelheim Please note: 2020-2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Scientific Medical Advisor relationship with United therapeutics Please note: 2021 Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Scientific Medical Advisor relationship with BMS Please note: 2019-present Added 04/20/2022 by Ganesh Raghu, value=Consulting fee Scientific Medical Advisor relationship with roche -genentech Please note: 2020++ Added 06/11/2022 by Ganesh Raghu, value=none sceintific medical advisor relationship with Fibrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Removed 06/11/2022 by Ganesh Raghu Scientific Medical Advisor relationship with FIbrogen Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Scientific Medical Advisor relationship with ROCHE -GENENTECH Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Scientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONR Removed 06/11/2022 by Ganesh Raghu Scientific Medical Advisor relationship with NITTO Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONE Scientific Medical Advisor relationship with BELLEROPHAN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=NONE DATA SAFETY MONITORIN BOARD relationship with AVALYN Please note: 2019 - Added 06/11/2022 by Ganesh Raghu, value=none Removed 06/11/2022 by Ganesh Raghu Scientific Medical Advisor relationship with AVALYN Please note: 2019- Added 06/11/2022 by Ganesh Raghu, value=none Grant relationship with Boehringer Ingelheim Please note: 2014 to present by Christopher Ryerson, value=Grant/Research Consultant relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2014-present by Christopher Ryerson, value=Royalty Consultant relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=Consulting fee Speaker/Speaker's Bureau relationship with Hoffmann-La Roche Please note: 2014-present by Christopher Ryerson, value=Royalty Speaker/Speaker's Bureau relationship with Cipla Ltd. Please note: 2020 by Christopher Ryerson, value=Royalty Advisory Committee Member relationship with Veracyte Please note: 2021 by Christopher Ryerson, value=Consulting fee Advisory Committee Member relationship with Astra Zeneca Please note: 2021 by Christopher Ryerson, value=Consulting fee Consultant relationship with Pliant Therapeutics Please note: ongoing Added 06/06/2022 by Christopher Ryerson, value=Consulting fee Advisory Committee Member relationship with veracyte Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting fee Advisory Committee Member relationship with genentech Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting fee Advisory Committee Member relationship with united therapeutics Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2020-2022 Added 06/21/2022 by Mary Beth Scholand, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Advisory Committee Member relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche Please note: 2019-2022 Added 06/21/2022 by Athol Wells, value=Consulting fee Advisory Committee Member relationship with Veracyte Please note: May 2022 Added 06/21/2022 by Athol Wells, value=Consulting fee