Molecular predictors of minimal residual disease in newly diagnosed multiple myeloma treated with quadruplet therapy.

Genomic, transcriptomic, and epigenomic features predict measurable residual disease in newly diagnosed multiple myeloma treated with quadruplet therapy, with an AUC of 0.77.

• Why it matters: Identifying molecular predictors of treatment response is crucial because response heterogeneity affects patient outcomes, and current methods lack precision in guiding early therapy decisions.
• What they did: Researchers analyzed 423 tumor samples from NDMM patients using integrated multiomic profiling, including whole-genome sequencing, gene expression, and DNA methylation, to find associations with MRD status after quadruplet induction therapy.
• The result: Genomic instability, driver gene alterations, and specific transcriptomic and epigenomic signatures were linked to MRD outcomes, enabling the development of a multimodal model that predicts MRD with higher accuracy than clinical or single-omic models.