Blood DNA markers at diagnosis predicted survival in 321 patients with multiple myeloma

Study title: Prognostic Significance of Cell-Free DNA Derived 5-Hydroxymethylcytosine Signatures in Newly Diagnosed Multiple Myeloma

In a prospective study of 321 patients with newly diagnosed multiple myeloma enrolled between 2010 and 2017, investigators measured 5-hydroxymethylcytosine modifications in cell-free DNA collected at diagnosis and built an 18-gene weighted prognostic score using elastic net Cox modeling and machine learning.

Read the study abstract

While survival outcomes in multiple myeloma (MM) have improved with contemporary combination therapies, predicting disease trajectories for individual patients at diagnosis remains a significant challenge. We investigate the prognostic value of a noninvasive biomarker-cell-free DNA (cfDNA)‑derived 5-hydroxymethylcytosine (5hmC) signature-in newly diagnosed MM, aiming to improve risk stratification at diagnosis. In this prospective cohort study, 321 patients with newly diagnosed MM were enrolled between 2010 and…

By the Truvace deskJuly 24, 20261 min read1 sourceEvidence: Moderate · 60/100 — Observational study · n = 321 · 1 independent sourcePeer-reviewedTRV-2026-0554· cite & verify

Prognostic Significance of Cell-Free DNA Derived 5-Hydroxymethylcytosine Signatures in Newly Diagnosed Multiple Myeloma — "Downtown Nassau - 2025 - Doctors Hospital (2)" by Bluerasberry is licensed under CC BY 4.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.

In brief

The score provided independent prognostic information for overall survival and progression-free survival in a validation set, which matters for noninvasive risk stratification at diagnosis, but the authors note that independent validation in contemporary treatment settings is still required before clinical adoption.

Main points

Prospective cohort of 321 newly diagnosed multiple myeloma patients enrolled 2010-2017 with follow-up through 2022 and median follow-up 70.5 months.
Genome-wide 5hmC modifications in gene bodies were profiled from cfDNA collected at diagnosis and compared to bone marrow-derived tumor cells.
Elastic net regularization with Cox model identified 18 key genes to build a weighted prognostic score validated in a held-out validation set.
During follow-up 127 deaths occurred and the score remained associated with OS and PFS at 24-, 48-, and 72-month follow-up periods.

The gain

A machine-learning derived weighted score from 18 cfDNA 5hmC-modified genes at diagnosis predicted overall and progression-free survival in newly diagnosed multiple myeloma after adjusting for stage and other clinical factors.

The rundown

Researchers profiled genome-wide 5hmC in cfDNA at diagnosis from 321 newly diagnosed MM patients and used elastic net regularized Cox modeling to select 18 genes for a weighted prognostic score.

In validation, the score was independently associated with overall survival and progression-free survival after controlling for stage, LDH and treatment type, and associations persisted at 24, 48 and 72 months.