Evidence for the Monitoring of Minimal Residual Disease Dynamics to Guide Clinical Practice in Patients with Multiple Myeloma

Multiple myeloma (MM) is a heterogeneous cancer that remains incurable. After treatment, the presence of residual myeloma clonal cells, or minimal residual disease (MRD), leads to tumor recurrence (relapse) and treatment failure (refractory disease). Strong clinical evidence indicates MRD is a surrogate marker of survival in patients with MM and is of important prognostic value in disease management. MRD status is dynamic and longitudinal changes in MRD status have different clinical implications. For example, sustained MRD negativity (undetectable MRD) has been associated with greatly improved survival outcomes, whereas the loss of MRD negativity is associated with disease progression. Although research on the prognostic impact of MRD dynamics in real world clinical practice is ongoing, several major concerns remain to be addressed before implementing the monitoring of MRD dynamics and MRD-guided therapeutic decision making in everyday clinical practice in the management of MM. In this review, we discuss the prognostic and clinical value of MRD dynamics, the evidence from literature for MRD-guided clinical decision making, and the challenges around implementing monitoring of MRD dynamics into clinical practice. Multiple myeloma (MM) is a type of cancer that develops in the bone marrow, in which cancerous plasma cells (or specialized white blood cells) multiply and replace the normal plasma cells that fight infections. After completing treatment, patients with MM may sometimes have minimal residual disease (MRD) or a small number of remaining cancerous plasma cells in the bone marrow, even if they show no other signs or symptoms of disease (i.e., have achieved remission). When treating MM, testing for MRD can help clinicians to predict the patient’s future risk of disease recurrence (or relapse) and may guide the decision-making process. The changes in the presence or absence of MRD over time (or MRD dynamics) are important for predicting these risks. For example, patients with undetectable cancer cells for a long period of time (i.e., sustained MRD negativity) have a much greater likelihood of survival than those in whom MRD is initially absent but cancer cells are later detected (i.e., shift from MRD-negative to MRD-positive), who are more likely to experience disease relapse or worsening. Monitoring MRD dynamics requires the use of highly sensitive testing techniques, such as next-generation sequencing, next-generation flow cytometry, and mass spectrometry. There are several questions regarding the role of monitoring MRD dynamics in predicting disease relapse and prognosis, as well as knowledge gaps around its use in routine clinical practice. Ongoing research may help to optimize the monitoring MRD dynamics to enable its widespread use and improve the management of patients with MM.