Potential future direction of measurable residual disease evaluation in multiple myeloma

Multiple myeloma remains an incurable disease plagued by high relapse rates. Deeper and more sustainable responses, however, have been consistently shown to improve outcomes and could eventually pave the way to achieving a cure. aur understanding of disease response has surpassed complete response (CR), because the current definitions are suboptimal, and the treatment goal should aim even beyond stringent CR, toward molecular and flow CR, that is, measurable residual disease (MRD) negativity. It has been more than 20 years since the discrepancy in the outcome between patients in CR with and without MRD has been demonstrated, and the field has come a long way from multiparameter flow cytometry to next-generation flow and next-generation sequencing, able to detect up to a limit of detection of a single myeloma cell from 1 million healthy counterparts. This review aims to summarize the current available data regarding MRD but also its potential future use as a coprimary outcome both in clinical and trial settings as a survival surrogate as well as its use to evaluate treatment efficacy and for adaptive response-based and early-rescue therapy. Furthermore, we discuss whether these concepts are applicable in different settings (eg, newly diagnosed and relapsed/ refractory myeloma, patients who are eligible and ineli-gible for tansplant, and standard-and high-risk disease).

Automated summary

Multiple myeloma is an incurable disease with high relapse rates. Deeper and more sustainable responses have been shown to improve outcomes and potentially lead to a cure. Current definitions of disease response are suboptimal, and the aim should be to measure measurable residual disease negativity. Advanced techniques have allowed the detection of a single myeloma cell among a million healthy cells.