Review Envisions MRD as Future Coprimary Endpoint and Treatment Adaptation Tool in Myeloma
This Blood review traces two decades of MRD evolution in multiple myeloma, from early multiparameter flow cytometry to next-generation flow and sequencing methods capable of detecting one myeloma cell per million. The authors argue for MRD as a coprimary trial endpoint and survival surrogate, and explore its potential for adaptive response-based therapy, early rescue strategies and treatment de-escalation across both transplant-eligible and transplant-ineligible settings.
The original study
Potential future direction of measurable residual disease evaluation in multiple myeloma.
- Authors
- Mohty M, Avet-Loiseau H, Malard F, Harousseau JL
- Journal
- Blood
- Type
- Review, Journal Article, Research Support, Non-U.S. Gov't
- PMID
- 37471603
Original abstract
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. Our 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 ineligible for tansplant, and standard- and high-risk disease).