Potential future direction of measurable residual disease evaluation in multiple myeloma

Abstract

Multiple myeloma remains an incurable disease plagued by high relapse rates. Deeper and more sustainable responses however, have been consistently shown to improve outcome and could eventually pave the way to achieving cure. Our understanding of disease response has surpassed complete response (CR) as the current definitions are suboptimal, and treatment goal should aim even beyond stringent CR, towards molecular and flow CR, i.e., measurable residual disease (MRD). It has been more than 20 years since the discrepancy in 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 (NGF) and next-generation sequencing (NGS), able to detect up to a limit of detection of a single myeloma cell from one million normal counterparts. This perspective review aims to summarize the current available data regarding MRD, but also its potential future use as a co-primary 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 discussed whether these concepts are applicable in different settings (eg. newly diagnosed and relapsed/refractory myeloma, transplant-eligible and transplant-ineligible patients, and standard- and high-risk disease).