Minimal Residual Disease in Multiple Myeloma: Past, Present, and Future

Simple Summary The assessment of responses is critical in patients diagnosed with multiple myeloma. Nowadays, one of the most informative parameters to discriminate responses to treatment and prognosis is minimal residual disease (MRD). Several strategies may be used to detect and quantify MRD; some of them have been widely used and standardized, but we can find additional strategies lacking such an extensive validation process. Here, we present a summary of the current state of the art of MRD detection in multiple myeloma and future directions in the field. Responses to treatment have improved over the last decades for patients with multiple myeloma. This is a consequence of the introduction of new drugs that have been successfully combined in different clinical contexts: newly diagnosed, transplant-eligible or ineligible patients, as well as in the relapsed/refractory setting. However, a great proportion of patients continue to relapse, even those achieving complete response, which underlines the need for updated response criteria. In 2014, the international myeloma working group established new levels of response, prompting the evaluation of minimal residual disease (MRD) for those patients already in complete or stringent complete response as defined by conventional serological assessments: the absence of tumor plasma cells in 100,000 total cells or more define molecular and immunophenotypic responses by next-generation sequencing and flow cytometry, respectively. In this review, we describe all the potential methods that may be used for MRD detection based on the evidence found in the literature, paying special attention to their advantages and pitfalls from a critical perspective.