M1. Clinical studies of fungal infections

Oral Abstract Submission

2886 - Retrospective Case-Control Study of the Performance of the Karius Test, a Plasma Microbial Cell-Free DNA Next-Generation Sequencing Test, to Detect Invasive Mold Infections in Hematopoietic Cell Transplant Recipients with Pneumonia

Co-Author(s)

• JH

  Joshua A. Hill, MD

  Assistant Memeber
  Fred Hutchinson Cancer Research Center; University of Washington
  Seattle, WA

  Disclosure: Amplyx: Consultant
  Karius: Grant/Research Support
  Nohla therapeutics: Consultant
  Shire: Grant/Research Support
• DH

  David K. Hong, MD

  Vice President, Medical Affairs and Clinical Development
  Karius, Inc
  Mountain View, CA

Presenting Author(s)

• SD

  Sudeb Dalai, MD

  Medical Director
  Karius, Inc
  Redwood City, CA

  Disclosure: Karius, Inc.: Employee

Co-Author(s)

• CH

  Carine Ho, MD

  Clinical Research Associate
  Karius, Inc
  Redwood City, CA

  Disclosure: Nothing to disclose
• DH

  Desiree D. Hollemon, MSN, MPH

  Head of Clinical Affairs
  Karius, Inc
  Redwood City, CA

  Disclosure: Karius, Inc. : Consultant
• LB

  Lily Blair, PhD

  Bioinformaticist
  Karius, Inc
  Redwood City, CA

  Disclosure: Karius, Inc.: Employee
• TS

  Terry Stevens-Ayers, MSc

  Research Technician
  Fred Hutchinson Cancer Research Center; University of Washington
  Seattle, WA

  Disclosure: Nothing to disclose
• 

  Michael Boeckh, MD PhD

  Member
  Fred Hutchinson Cancer Research Center
  Seattle, WA

  Disclosure: Ablynx: Consultant, Grant/Research Support
  Ansun Biopharma: Consultant, Grant/Research Support
  Astellas: Consultant, Grant/Research Support
  Bavarian Nordic: Consultant
  Chimerix: Consultant, Grant/Research Support
  Gilead: Consultant, Grant/Research Support
  GlaxoSmithKline: Consultant
  Helocyte: Consultant
  Janssen: Consultant, Grant/Research Support
  Lophius: Grant/Research Support
  Merck: Consultant, Grant/Research Support
  Moderna: Consultant
  Shire: Consultant, Grant/Research Support
  Vir Bio: Consultant, Grant/Research Support
• CF

  Cynthia E. Fisher, MD, MPH

  Assistant Professor
  University of Washington
  Seattle, WA

  Disclosure: Karius, Inc.: Grant/Research Support

Background :

Pulmonary invasive mold infections (IMI) cause significant morbidity and mortality after hematopoietic cell transplant (HCT). Non-invasive diagnostic options are limited, particularly for non-Aspergillus (non-Asp) molds. Given differences in activity and toxicities of antifungals, early diagnosis and targeting of specific IMI is important. We evaluated the performance of the Karius Test, a plasma microbial cell-free DNA next-generation sequencing (NGS) test, for detecting IMI in HCT recipients.

Methods :

We conducted a retrospective case-control study of 24 HCT recipients with proven non-Asp pulmonary IMI, 51 probable/proven Aspergillus pulmonary IMI, and 20 controls with non-fungal pulmonary infections. All subjects had plasma obtained within 14 days of diagnosis. Workup included bronchoalveolar lavage (BAL) and/or biopsy, with fungal stains/culture and galactomannan testing of BAL and serum. Plasma cell-free DNA was extracted and NGS performed (Karius, Redwood City, CA). Human reads were removed and remaining sequences aligned to a curated database including over 300 fungi. Organisms present above a predefined significance threshold were reported. A higher sensitivity research-use only pipeline was also used. Analysis of sequencing data was blinded to all clinical data.

Results : We identified pathogenic molds in 19/24 (79%) of subjects with proven non-Asp IMI, including Mucor, Rhizomucor, Scedosporium, Rhizopus, and Cunninghamella spp. In Aspergillus proven/probable IMI, A. fumigatus was identified in 13.7% (7/51) of subjects. In 3 other subjects with proven/probable aspergillosis, we also identified Rhizomucor miehei and R.pusillus, and Cunninghamella, consistent with clinical findings. Use of an optimal-sensitivity pipeline identified an additional 9 subjects with Aspergillus spp. and other pathogenic molds, increasing detection of molds to 37.3% (19/51). Specificity for molds in negative samples was 100% (20/20).

Conclusion :

The Karius plasma NGS test is a non-invasive means of detecting IMI with high sensitivity for non-Aspmolds in HCT recipients with pulmonary disease. Further assay optimization may increase sensitivity for Aspergillus. This may be a useful adjunctive test for diagnosing IMI, and larger studies should be conducted.