Plasma microbial cell-free DNA (KARIUS) testing to diagnose invasive mold infections in patients with cancer

Author:

Deepa Nanayakkara (US)

Abstract:

Background:
Invasive mold infections (IMIs) cause significant morbidity and mortality in patients with malignancy, particularly in those with hematologic malignancy and/or after hematopoietic cell transplantation (HCT). We evaluated the utility of plasma microbial cell-free DNA (mcfDNA; KARIUS) testing to diagnose IMIs and its correlation with standard of care (SOC) testing at our institution.
Methods:
We performed a retrospective chart review of patients in whom an Aspergillus and/or Mucorales species was detected on KARIUS testing from 1/1/2021 to 6/20/2023. We collected the following data on SOC testing: serum Aspergillus galactomannan (AGM), bronchoalveolar lavage fluid (BALF) fungal stain and culture, AGM, Mucorales PCR, and cytology, and tissue biopsy pathology, fungal stain and culture. We also reviewed demographics, underlying malignancy, classification of probable or proven IMI per EORTC/MSGERC criteria, and time to diagnosis of IMI with KARIUS testing.
Results:
Seventy-six (76) patients with positive KARIUS test for Aspergillus and/or Mucorales species were identified. All had host, clinical and radiographic features suggestive of an IMI. Seventy-four had a hematological malignancy, one lung cancer, and one thymoma. Sites of IMI were lungs (63), rhino-orbital (5), central nervous system (1), cutaneous (1), and multiple sites (6).
KARIUS test identified Aspergillus species alone in 39 patients (61% were Aspergillus fumigatus), Mucorales alone in 33 patients (59% Rhizopus microsporus and Rhizopus oryzae) and Aspergillus and Mucorales co-infection in 4 patients. There was added value of KARIUS testing: for Aspergillus, 33 patients had proven/probable infection with SOC testing and 6 (15.4%) additional cases were identified by KARIUS test. For Mucorales, 21 patients had proven/probable infection by SOC tests and 12 (36.3%) additional cases were identified by KARIUS test. KARIUS testing led to diagnosis at genus and species level versus SOC testing in 57/76 patients (75%). In 31 patients, KARIUS testing was ordered on the same day as or before pursuing diagnostic modalities per EORTC/MSGERC criteria, which led to an earlier diagnosis in 17 patients (54.8%) within this sub-group by a median of 2 days. In 18 patients, KARIUS testing detected the only positive microbiological result and SOC testing was deferred in 7 of these patients due to tenuous clinical status or death. There were 12 instances of mixed infections where KARIUS test failed to detect a pathogen that was otherwise demonstrated by SOC testing: Aspergillus (6), Mucor (2), Pseudallescheria boydii (2), Curvularia (1), Alternaria (1).
Conclusions:
mcfDNA (KARIUS) testing may lead to improved diagnostic yield with rapid turnaround time compared to SOC testing in this sub-group of patients with high pre-test probability of IMI. More importantly, it can identify pathogen to genus/species level that may have an impact on antifungal treatment choices. However, at this stage, SOC testing is still very important and cannot be replaced by mcfDNA testing.

Abstract Number: 25

Conference Year: 2024

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