Controversies in the assessment of minimal residual disease in multiple myeloma: clinical significance of minimal residual disease negativity using highly sensitive techniques.

Minimal residual disease (MRD) assessment has gained importance in the response evaluation of multiple myeloma. As discussed in part 1 of this two-part series, techniques such as multiparameter flow cytometry, polymerase chain reaction, and next-generation sequencing, of both bone marrow and peripheral blood, have the potential to achieve a high level of sensitivity, up to 1 in 10(-6) cells, enabling analysis of genetically diverse subclones. Here, we review the clinical utility of MRD assessment using these techniques. Specifically, we review the association between MRD-negativity and progression-free or overall survival in various clinical settings (post-induction, post-auto or allo-stem cell transplant, transplant ineligible, maintenance, and relapsed/refractory). Currently, the goal of assessing MRD in multiple myeloma (MM) is to allow for a risk-stratified approach to therapy and for earlier identification of response to novel agents, particularly in the setting of clinical trials.