To characterize newly diagnosed multiple myeloma across genomic, transcriptomic and DNA methylation layers in a uniformly treated trial cohort, and identify molecular factors associated with measurable residual disease (MRD) after quadruplet induction.
Approach:
Study cohort: The ancillary MIDAS study profiled 423 patients using whole-genome sequencing, RNA sequencing and whole-genome enzymatic methylation sequencing; MRD-predictor analyses were limited to enrolled patients.
Treatment and response: Patients received Isa-KRd induction. Post-induction MRD was assessed in 368 enrolled patients, with negativity evaluated at thresholds of 10−6 and 10−5.
Molecular analysis: The investigators integrated genomic, transcriptomic and methylation profiles and examined associations between molecular groups and MRD status.
Key Findings:
Gene-expression classification identified eight molecular groups associated with genomic alterations; no distinct proliferation subgroup was detected, with proliferation scores distributed continuously across clusters.
Post-induction MRD was negative in 44.8% of assessed patients at 10−6 and 59.8% at 10−5.
MRD-negativity rates differed significantly by expression group and remained associated after adjustment for clinical covariates.
MRD negativity was least frequent in the CD2 and MF groups and most frequent in HP1, HP3 and MS.
Expression-group associations with MRD remained significant before maintenance, although MRD-negativity rates partially converged over time.
Differential expression analysis identified 170 genes upregulated in MRD-positive samples, including CCND1 and MAFA.
Interpretation:
In this uniformly treated MIDAS cohort, transcriptomic subgroup was associated with MRD status after quadruplet induction. The supplied context reports integrated profiling and MRD associations but does not provide the full results for genomic or methylation predictors.
Limitations:
The supplied article context ends during the differential-expression results, so later findings and the authors’ full interpretation are unavailable.
MRD-predictor analyses were restricted to enrolled patients; post-induction MRD data were available for 368 of 394 enrolled patients.
The multiomic subset modestly overrepresented patients with higher ISS stages and greater bone marrow plasma-cell burden compared with patients without multiomic data.
by Florence Magrangeas, Mia Cherkaoui, Victor Bessonneau-Gaborit, Jennifer Derrien, Céline Chevalier, Catherine Guérin-Charbonnel, Benjamin Diamond, Mehmet Kemal Samur, Cyrille Hulin, Denis Caillot, Lionel Karlin, Bertrand Arnulf, Ola Landgren, Nikhil C. Munshi, Hervé Avet-Loiseau, Ludovic Martinet, Jill Corre, Aurore Perrot, Philippe Moreau, Cyrille Touzeau, Stéphane Minvielle, Eric Letouzé
Breast cancer screening has traditionally been organized around two principal variables: when mammography should begin and how frequently it should be performed.
