Matched marrow and blood profiling reveals compartment- and feature-specific liquid-biopsy signals in multiple myeloma
- 1Princess Margaret Cancer Centre, University Health Network
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.
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BibTeX
@misc{abelman2026matched,
title = {{Matched marrow and blood profiling reveals compartment- and feature-specific liquid-biopsy signals in multiple myeloma}},
author = {D. D. Abelman and J. Eagles and S. Pedersen and D. S. Scott and A. Danesh and J. P. Bruce and S. D. Prokopec and A. Wong and E. N. Wei and S. Shah and D. White and I. Sandhu and K. Song and A. Murugesan and A. Reiman and S. Trudel and T. J. Pugh},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.26358882},
url = {https://www.medrxiv.org/content/10.64898/2026.09.09.26358882v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Matched marrow and blood profiling reveals compartment- and feature-specific liquid-biopsy signals in multiple myeloma
AU - D. D. Abelman
AU - J. Eagles
AU - S. Pedersen
AU - D. S. Scott
AU - A. Danesh
AU - J. P. Bruce
AU - S. D. Prokopec
AU - A. Wong
AU - E. N. Wei
AU - S. Shah
AU - D. White
AU - I. Sandhu
AU - K. Song
AU - A. Murugesan
AU - A. Reiman
AU - S. Trudel
AU - T. J. Pugh
PY - 2026
DA - 2026/09/09
PB - medRxiv
DO - 10.64898/2026.09.09.26358882
UR - https://www.medrxiv.org/content/10.64898/2026.09.09.26358882v1
AB - 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.
ER -