Minimal Residual Disease Negativity as the Primary Goal of Multiple Myeloma Therapy

Measurable (or minimal) residual disease (MRD) testing offers critical prognostic insight in multiple myeloma (MM), surpassing conventional response criteria. While bone-marrow-based assays are most commonly performed, MRD assessment in peripheral blood and advanced imaging may add complementary value. A comprehensive approach, integrating serial MRD testing across compartments, may offer the most accurate appraisal of disease burden. MRD has been validated as a surrogate endpoint for accelerated approval (AA) of MM therapies and is increasingly adopted as a key clinical trial endpoint. Ongoing phase 3 trials are using MRD status to tailor consolidation and maintenance strategies, and emerging evidence supports its role in guiding treatment de-escalation, including discontinuation of maintenance therapy. However, barriers remain to implementing MRD as a treatment goal, including cost, complexity of interpreting results, and uncertainty around the optimal timing for guiding decision-making. Moreover, there is a paucity of data on the use of MRD resurgence to prompt changes in therapy. While MRD negativity represents a compelling endpoint in both clinical practice and research, prospective randomized studies will help to better elucidate how best to incorporate MRD into the MM treatment paradigm.