Matched marrow and blood profiling reveals compartment- and feature-specific liquid-biopsy signals in multiple myeloma
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Multiple myeloma is bone-marrow-predominant, motivating marrow plasma cell-free DNA (cfDNA) as a tumor-proximal liquid biopsy. We tested whether marrow plasma cfDNA better represents the myeloma genome than peripheral blood cfDNA by profiling matched marrow plasma cells and both cfDNA compartments from 74 patients across 372 cfDNA sample time points. Tumor fractions correlated between compartments (r=0.84), but marrow plasma cfDNA was not a superior surrogate: peripheral-blood cfDNA matched or exceeded marrow-plasma cfDNA for marrow-defined CNA and mutation recovery (77.4% vs 72.0%; 69.2% vs 65.4%), with high specificity. Disease-associated features were detected in 69/74 peripheral-blood and 68/74 marrow-plasma profiles. BCR clonotypes were the highest-recovery feature, with BM-dominant clonotypes recovered in 31/34 callable profiles per compartment. At high tumor fraction, adverse-lesion sensitivity reached 100% in both cfDNA compartments. Marrow plasma cfDNA showed distinct, handling-sensitive fragmentomic architecture (LOOCV AUC=0.910), demonstrating performance depends on compartment, biomarker class, tumor fraction and processing context.
Source: medRxiv
Institutions: University Health Network, University of Toronto, Princess Margaret Cancer Centre, University of New Brunswick, Dalhousie University, Queen Elizabeth II Health Sciences Centre, Cross Cancer Institute, Vancouver General Hospital, Saint John Regional Hospital, Ontario Institute for Cancer Research
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7213047095