Undetectable Minimal Residual Disease in Multiple Myeloma: Bridging the Gap Between Clinical Trials and Real-life Application

Much evidence supports the assessment of minimal residual disease (MRD) status in the clinical management of multiple myeloma (MM). Using highly sensitive next-generation flow cytometry and next-generation sequencing tests to detect MRD enables clinicians to evaluate the depth of response and therefore the prognosis of patients with MM as achieving deep and sustained (≥ 12 months) undetectable MRD correlates with prolonged survival in patients with MM. Because of this, undetectable MRD (also referred to as MRD-negativity) has been recognized and approved by the FDA as an early endpoint in clinical trials to accelerate regulatory approval of new treatments for MM. However, many questions remain around how (methods, sensitivity levels), who (all patients vs. those achieving complete/partial response), and when to test in relation to treatment phases, defining the optimal duration for sustained undetectable MRD, and how MRD can be used to guide treatment strategies in clinical practice. This narrative review has examined data from key clinical trials in MM to analyze the implementation of MRD testing in the newly-diagnosed and relapsed/refractory MM settings. We have also summarized trials that test MRD-driven approaches.