Baseline molecular features of multiple myeloma tumors are associated with whether patients achieve minimal residual disease (MRD) negativity after quadruplet induction therapy, according to a multiomic analysis published in Nature Medicine. The study examined samples from patients with newly diagnosed multiple myeloma who received isatuximab, carfilzomib, lenalidomide and dexamethasone, followed by consolidation treatment guided by MRD status.
The research focused on genomic, transcriptomic and epigenetic characteristics present before treatment and their relationship to MRD status after induction. MRD refers to the small number of cancer cells that remain in the body after treatment and can be detected only with highly sensitive laboratory methods. Achieving MRD negativity is widely considered an important treatment goal in multiple myeloma, as it is associated with deeper responses and improved long-term outcomes.
The findings suggest that molecular profiling at diagnosis could help identify patients more or less likely to achieve MRD negativity with this quadruplet regimen. The analysis integrated multiple layers of molecular data, including DNA-level genomic features, RNA-level transcriptomic patterns and epigenetic modifications, to build a more complete picture of the tumor biology associated with treatment response.
The study adds to a growing body of research aimed at personalizing multiple myeloma treatment. Quadruplet regimens combining a CD38-directed antibody, a proteasome inhibitor, an immunomodulatory drug and a corticosteroid have become a standard of care for many newly diagnosed patients, but responses vary widely. Tools that predict depth of response could eventually help clinicians tailor treatment intensity and duration.
The authors report associations between baseline molecular features and MRD status after induction, but further research is needed to validate these predictors in larger and more diverse patient populations. The work also highlights the potential of multiomic approaches to uncover biological mechanisms that influence how myeloma cells respond to combination therapy.
The study was published online in Nature Medicine on 19 October 2026.
14
